Variant 2-75493337-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135032.2(EVA1A):c.358C>T(p.Arg120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVA1A	NM_001135032.2 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	4/4	ENST00000393913.8
EVA1A	NM_001369524.1 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	6/6
EVA1A	NM_001369525.1 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	5/5
EVA1A	NM_032181.3 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1A	ENST00000393913.8 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	4/4	1	NM_001135032.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 12, 2022

The c.358C>T (p.R120C) alteration is located in exon 4 (coding exon 2) of the EVA1A gene. This alteration results from a C to T substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a cysteine (C). 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

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T;T;T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.50

T;T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

3.3

M;M;M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.4

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.011

D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;.

Polyphen

1.0

D;D;D;.;D;.

Vest4

0.68

MutPred

0.32

Loss of MoRF binding (P = 0.0457);Loss of MoRF binding (P = 0.0457);Loss of MoRF binding (P = 0.0457);.;Loss of MoRF binding (P = 0.0457);Loss of MoRF binding (P = 0.0457);

MVP

0.76

MPC

1.4

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over