Variant 12-102855146-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000277.3(PAH):c.696G>A(p.Gln232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,612,432 control chromosomes in the GnomAD database, including 297,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32291 hom., cov: 33)

Exomes 𝑓: 0.60 ( 265563 hom. )

Consequence

PAH
NM_000277.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.59

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-102855146-C-T is Benign according to our data. Variant chr12-102855146-C-T is described in ClinVar as [Benign]. Clinvar id is 167414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-102855146-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PAH	NM_000277.3 linkuse as main transcript	c.696G>A	p.Gln232=	synonymous_variant	6/13	ENST00000553106.6	NP_000268.1
PAH	NM_001354304.2 linkuse as main transcript	c.696G>A	p.Gln232=	synonymous_variant	7/14		NP_001341233.1
PAH	XM_017019370.2 linkuse as main transcript	c.696G>A	p.Gln232=	synonymous_variant	6/7		XP_016874859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PAH	ENST00000553106.6 linkuse as main transcript	c.696G>A	p.Gln232=	synonymous_variant	6/13	1	NM_000277.3	ENSP00000448059	P1
PAH	ENST00000549111.5 linkuse as main transcript	n.792G>A		non_coding_transcript_exon_variant	6/6	1
PAH	ENST00000307000.7 linkuse as main transcript	c.681G>A	p.Gln227=	synonymous_variant	7/14	5		ENSP00000303500

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96994

AN:

151978

Hom.:

32266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.580

AC:

145665

AN:

251250

Hom.:

45197

AF XY:

0.573

AC XY:

77839

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.778

Gnomad AMR exome

AF:

0.704

Gnomad ASJ exome

AF:

0.547

Gnomad EAS exome

AF:

0.0903

Gnomad SAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.595

AC:

869087

AN:

1460334

Hom.:

265563

Cov.:

AF XY:

0.593

AC XY:

430734

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.704

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.0907

Gnomad4 SAS exome

AF:

0.570

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.583

GnomAD4 genome

AF:

0.638

AC:

97075

AN:

152098

Hom.:

32291

Cov.:

AF XY:

0.638

AC XY:

47427

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.774

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.0948

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.617

Hom.:

20498

Bravo

AF:

0.646

Asia WGS

AF:

0.397

AC:

1382

AN:

3478

EpiCase

AF:

0.587

EpiControl

AF:

0.591

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Phenylketonuria

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 16, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.27

DANN

Benign

0.50

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