Variant 2-75493369-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001135032.2(EVA1A):c.326A>T(p.Lys109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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=0.065835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVA1A	NM_001135032.2 linkuse as main transcript	c.326A>T	p.Lys109Met	missense_variant	4/4	ENST00000393913.8
EVA1A	NM_001369524.1 linkuse as main transcript	c.326A>T	p.Lys109Met	missense_variant	6/6
EVA1A	NM_001369525.1 linkuse as main transcript	c.326A>T	p.Lys109Met	missense_variant	5/5
EVA1A	NM_032181.3 linkuse as main transcript	c.326A>T	p.Lys109Met	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1A	ENST00000393913.8 linkuse as main transcript	c.326A>T	p.Lys109Met	missense_variant	4/4	1	NM_001135032.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251302

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.326A>T (p.K109M) alteration is located in exon 4 (coding exon 2) of the EVA1A gene. This alteration results from a A to T substitution at nucleotide position 326, causing the lysine (K) at amino acid position 109 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.0037

T;T;T;T;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.56

M_CAP

Benign

0.0058

MetaRNN

Benign

0.066

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.075

N;N;N;.;N;.

MutationTaster

Benign

0.92

N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.42

N;N;N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.24

T;T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T;.

Polyphen

0.053

B;B;B;.;B;.

Vest4

0.090

MutPred

0.30

Loss of methylation at K109 (P = 0.0075);Loss of methylation at K109 (P = 0.0075);Loss of methylation at K109 (P = 0.0075);.;Loss of methylation at K109 (P = 0.0075);Loss of methylation at K109 (P = 0.0075);

MVP

0.35

MPC

0.54

ClinPred

0.28

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.051

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