Variant rs1522306 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: PAH-specific ACMG/AMP criteria applied: BA1: MAF=0.49022 in ExAC. In summary this variant meets criteria to be classified as benign for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA145984/MONDO:0009861/006

Frequency

Genomes: 𝑓 0.36 ( 10523 hom., cov: 32)

Exomes 𝑓: 0.40 ( 116538 hom. )

Consequence

PAH
NM_000277.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:6O:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]

PAH links:

PAH (HGNC:):

PAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAH	NM_000277.3 linkuse as main transcript	c.969+43G>T		intron_variant		ENST00000553106.6	NP_000268.1	P00439A0A024RBG4
PAH	NM_001354304.2 linkuse as main transcript	c.969+43G>T		intron_variant			NP_001341233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAH	ENST00000553106.6 linkuse as main transcript	c.969+43G>T		intron_variant		1	NM_000277.3	ENSP00000448059.1		P00439

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54663

AN:

151902

Hom.:

10514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.0550

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.351

AC:

88020

AN:

250424

Hom.:

17196

AF XY:

0.359

AC XY:

48625

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.0555

Gnomad SAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.403

AC:

555142

AN:

1377846

Hom.:

116538

Cov.:

AF XY:

0.402

AC XY:

277660

AN XY:

690566

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.0463

Gnomad4 SAS exome

AF:

0.349

Gnomad4 FIN exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.384

GnomAD4 genome

AF:

0.360

AC:

54701

AN:

152020

Hom.:

10523

Cov.:

AF XY:

0.363

AC XY:

26937

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.0552

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.508

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.391

Hom.:

2255

Bravo

AF:

0.340

Asia WGS

AF:

0.233

AC:

810

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 22, 2013	- -

Phenylketonuria

Benign:2

Benign, reviewed by expert panel	curation	ClinGen PAH Variant Curation Expert Panel	Aug 10, 2018	PAH-specific ACMG/AMP criteria applied: BA1: MAF=0.49022 in ExAC; BP2: Observed in cis with R261Q. (PMID:24048906). In summary this variant meets criteria to be classified as benign for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BA1, BP2). -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.28

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over