Variant rs2037639 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP7BA1

This summary comes from the ClinGen Evidence Repository: The c.353-22C>T variant in PAH has a MAF of 0.7066 in the gnomAD East Asian population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA229520/MONDO:0009861/006

Frequency

Genomes: 𝑓 0.22 ( 4517 hom., cov: 31)

Exomes 𝑓: 0.25 ( 48672 hom. )

Consequence

PAH
NM_000277.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:8O:1

Conservation

PhyloP100: -0.216

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:

LOC124902999 (HGNC:):

LOC124902999 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP7

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PAH	NM_000277.3 linkuse as main transcript	c.353-22C>T	intron_variant	ENST00000553106.6	NP_000268.1
LOC124902999	XR_007063428.1 linkuse as main transcript	n.808-2307G>A	intron_variant, non_coding_transcript_variant
PAH	NM_001354304.2 linkuse as main transcript	c.353-22C>T	intron_variant		NP_001341233.1
PAH	XM_017019370.2 linkuse as main transcript	c.353-22C>T	intron_variant		XP_016874859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAH	ENST00000553106.6 linkuse as main transcript	c.353-22C>T		intron_variant		1	NM_000277.3	ENSP00000448059	P1

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33548

AN:

151976

Hom.:

4519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.274

AC:

68767

AN:

250962

Hom.:

11705

AF XY:

0.278

AC XY:

37735

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.707

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.247

AC:

352222

AN:

1425802

Hom.:

48672

Cov.:

AF XY:

0.250

AC XY:

178113

AN XY:

711592

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.221

AC:

33549

AN:

152092

Hom.:

4517

Cov.:

AF XY:

0.224

AC XY:

16679

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.277

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.217

Hom.:

4312

Bravo

AF:

0.214

Asia WGS

AF:

0.432

AC:

1504

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Phenylketonuria

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 13, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, reviewed by expert panel	curation	ClinGen PAH Variant Curation Expert Panel	Mar 27, 2020	The c.353-22C>T variant in PAH has a MAF of 0.7066 in the gnomAD East Asian population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -

not provided

Benign:2Other:1

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	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.1

DANN

Benign

0.60

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