2-75518107-C-T

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

19

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]

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
EVA1ANM_001135032.2 linkc.34G>A p.Val12Met missense_variant Exon 3 of 4 ENST00000393913.8 NP_001128504.1 Q9H8M9
EVA1ANM_001369524.1 linkc.34G>A p.Val12Met missense_variant Exon 5 of 6 NP_001356453.1
EVA1ANM_001369525.1 linkc.34G>A p.Val12Met missense_variant Exon 4 of 5 NP_001356454.1
EVA1ANM_032181.3 linkc.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
EVA1AENST00000393913.8 linkc.34G>A p.Val12Met missense_variant Exon 3 of 4 1 NM_001135032.2 ENSP00000377490.3 Q9H8M9

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152164
Hom.:
0
Cov.:
32
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:
43
AN:
251046
Hom.:
0
AF XY:
0.000111
AC XY:
15
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:
99
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.0000564
AC XY:
41
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:
11
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
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.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.000165
AC:
20
Asia WGS
AF:
0.00202
AC:
7
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
T
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
N
LIST_S2
Benign
0.36
.;T;.;.;T;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.012
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L;L;L;.;.
PrimateAI
Benign
0.35
T
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
T
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.

Other links and lift over

dbSNP: rs112344664; hg19: chr2-75745233; API