Pubvar

12:103234177:C/T

GRCh37/hg19 position	12:103234177
GRCh38/hg38 position	12:102840399
Alleles (ref/alt)	C/T
dbSNP rsid	rs5030861
Gene symbol	PAH
Most severe consequence	splice_donor_variant
Flanking sequence	CCGAGTGGCCTCGTAAGGTGTAAATTACTTA[C/T]TGTTAATGGAATCAGCCAAAATCTTAAGCTG
HGVS	NM_000277.3:c.1315+1G>A NM_001354304.2:c.1315+1G>A

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Gene annotations

Transcript	Gene	Exon number	Consequence	HGVS cDNA	HGVS protein	Location	Protein location
NM_000277.3	PAH	-	splice_donor_variant	c.1315+1G>A	-	Intron 12
NM_001354304.2	PAH	-	splice_donor_variant	c.1315+1G>A	-	Intron 13

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Population frequency

Select populations: ALL LWK MKK YRI EUR FIN NFE CEU ASJ TSI EAS SAS CHB HAN CHD JPT AFR AMR ASW GIH MEX OTH

Database	Population	AC	AN	Hom	AF
ExAC	ALL	42	121228	0	0.000346
	FIN	0	6596	0	0
	NFE	40	66664	0	0.000600
	EAS	0	8650	0	0
	SAS	0	16508	0	0
	AFR	2	10404	0	0.000192
	AMR	0	11498	0	0
	OTH	0	908	0	0
gnomAD genomes	ALL	12	30952	0	0.000387697
	FIN	0	3492	0	0
	NFE	11	15006	0	0.00073304
	ASJ	0	302	0	0
	EAS	0	1608	0	0
	AFR	1	8724	0	0.000114626
	AMR	0	838	0	0
	OTH	0	982	0	0
gnomAD exomes	ALL	96	246188	0	0.000389946
	FIN	0	22296	0	0
	NFE	92	111696	0	0.000823664
	ASJ	0	9850	0	0
	EAS	0	17244	0	0
	SAS	0	30782	0	0
	AFR	2	15302	0	0.000130702
	AMR	1	33538	0	2.98169e-05
	OTH	1	5480	0	0.000182482
HRC	ALL	45	64976	-	0.000692563

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Functional predictions

Tool	Score	Prediction
MutationTaster	1	disease_causing
CADD	3.732707	-

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View on UCSC genome browser

Conservation

Conservation scores are retrieved from UCSC genome browser. The conservation levels are defined by simple cutoff values. If the conservation levels do not agree with each other, you can manually check whether this variant is conserved with UCSC genome browser.

Method	Score	Level
GERP++	5.33	Conserved
phastCons46way primates	0.591	Conserved
phastCons46way placental	0.996	Highly conserved
phastCons100way vertebrates	1.000	Highly conserved
phyloP46way primates	0.561	Conserved
phyloP46way placental	2.664	Conserved
phyloP100way vertebrates	7.049	Conserved

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ClinVar

Accession	Clinical significance	Date last evaluated	Review status	Method	Disease name	Disease symbol	Disease inheritance	Pubmed
RCV000000606	Pathogenic	2018-08-05	reviewed by expert panel	clinical testing	Phenylketonuria	PKU	Autosomal recessive inheritance	12655544 3008810 2014036 22526846 24190797 20301677 24941924 17935162 9634518 26542770 3615198 25741868 25525159 17576681 25596310 11914042 28492532 9536098 23500595 24368688 17502162 23559577 21228398
RCV004799176	Pathogenic	2020-01-21	criteria provided, single submitter	clinical testing	Pituitary hormone deficiency, combined, 2	-	-	-
RCV003407249	Pathogenic	2023-10-12	criteria provided, single submitter	clinical testing	PAH-related disorder	-	-	25741868
RCV000622610	Pathogenic	2021-01-05	criteria provided, single submitter	clinical testing	Inborn genetic diseases	-	-	25525159 25087612 3008810
RCV000078510	Pathogenic	2024-05-01	criteria provided, multiple submitters, no conflicts	clinical testing	not provided	-	-	22975760 3008810 23500595 26467025 34828281 24941924 17935162 9634518 26542770 3615198 25087612 25741868 25525159 37189584 2014036 11999982 25596310 36646061 24368688 33375644 23559577 23430918 21228398

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InterVar

InterVar is a software tool for clinical interpretation of genetic variants by the ACMG/AMP 2015 guideline. The eveidence tags that variant met are highlighted. Please note that evidence tags with need to be evaluated manually.

Class: Pathogenic

	Benign		Pathogenic
	Strong	Supporting	Supporting	Moderate	Strong	Very Strong
Population data	BA1 BS1 BS2			PM2	PS4
Computational and predictive data		BP1 BP3 BP4 BP7	PP3	PM4 PM5	PS1	PVS1
Functional data	BS3		PP2	PM1	PS3
Segregation data	BS4		PP1	PP1	PP1
De novo data				PM6	PS2
Allelic data		BP2		PM3
Other database		BP6	PP5
Other data		BP5	PP4