Variant 22-36815175-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000417718.7(PVALB):c.122C>T(p.Ala41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,614,110 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 38 hom. )

Consequence

PVALB
ENST00000417718.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

PVALB (HGNC:9704): (parvalbumin) The protein encoded by this gene is a high affinity calcium ion-binding protein that is structurally and functionally similar to calmodulin and troponin C. The encoded protein is thought to be involved in muscle relaxation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PVALB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021724403).

BP6

Variant 22-36815175-G-A is Benign according to our data. Variant chr22-36815175-G-A is described in ClinVar as [Benign]. Clinvar id is 781616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1646/152250) while in subpopulation AFR AF= 0.0383 (1592/41530). AF 95% confidence interval is 0.0368. There are 27 homozygotes in gnomad4. There are 761 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2 linkuse as main transcript	c.122C>T	p.Ala41Val	missense_variant	2/4	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3 linkuse as main transcript	c.122C>T	p.Ala41Val	missense_variant	3/5		NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7 linkuse as main transcript	c.122C>T	p.Ala41Val	missense_variant	2/4	1	NM_001315532.2	ENSP00000400247	P1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1642

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00272

AC:

683

AN:

251448

Hom.:

AF XY:

0.00196

AC XY:

266

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00110

AC:

1611

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

688

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.0108

AC:

1646

AN:

152250

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

761

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0383

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.0126

ESP6500AA

AF:

0.0377

AC:

166

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00345

AC:

419

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;T;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.20

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.043

D;D;T;D

Sift4G

Benign

0.30

T;T;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.26

MVP

0.35

MPC

0.26

ClinPred

0.013

GERP RS

1.7

Varity_R

0.068

gMVP

0.46

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