Genetic Variant EVA1A:p.Val12Met (chr2-75518107-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001135032.2(EVA1A):c.34G>A(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.671

Variant links:

Genes affected

EVA1A (HGNC:25816): (eva-1 homolog A, regulator of programmed cell death) Predicted to be involved in apoptotic process and autophagy. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012169272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1A	NM_001135032.2 link	c.34G>A	p.Val12Met	missense_variant	Exon 3 of 4	ENST00000393913.8	NP_001128504.1	Q9H8M9
EVA1A	NM_001369524.1 link	c.34G>A	p.Val12Met	missense_variant	Exon 5 of 6		NP_001356453.1
EVA1A	NM_001369525.1 link	c.34G>A	p.Val12Met	missense_variant	Exon 4 of 5		NP_001356454.1
EVA1A	NM_032181.3 link	c.34G>A	p.Val12Met	missense_variant	Exon 3 of 4		NP_115557.1	Q9H8M9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1A	ENST00000393913.8 link	c.34G>A	p.Val12Met	missense_variant	Exon 3 of 4	1	NM_001135032.2	ENSP00000377490.3		Q9H8M9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251046

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34G>A (p.V12M) alteration is located in exon 3 (coding exon 1) of the EVA1A gene. This alteration results from a G to A substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.27

DANN

Benign

0.80

DEOGEN2

Benign

0.0055

T;T;T;T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.36

.;T;.;.;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.38

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;.;T

Polyphen

0.0010

B;B;B;B;.;.

Vest4

0.15

MVP

0.16

MPC

0.37

ClinPred

0.031

GERP RS

-10

Varity_R

0.014

gMVP

0.25

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