dbSNP rs1180391262: EVA1C:p.Cys42Arg (chr21-32412977-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_058187.5(EVA1C):c.124T>C(p.Cys42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C42G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.588

Publications

0 publications found

Variant links:

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EVA1C links:

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28674555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5 link	c.124T>C	p.Cys42Arg	missense_variant	Exon 1 of 8	ENST00000300255.7	NP_478067.2	P58658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7 link	c.124T>C	p.Cys42Arg	missense_variant	Exon 1 of 8	1	NM_058187.5	ENSP00000300255.2		P58658-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000468

AC:

AN:

149478

AF XY:

0.0000359

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000545

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1342848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

659954

African (AFR)

AF:

0.00

AC:

AN:

27730

American (AMR)

AF:

0.00

AC:

AN:

29340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22624

East Asian (EAS)

AF:

0.00

AC:

AN:

32146

South Asian (SAS)

AF:

0.00

AC:

AN:

70896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5410

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050098

Other (OTH)

AF:

0.00

AC:

AN:

54752

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.086

T;T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;L

PhyloP100

0.59

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.24

Sift

Benign

0.079

T;D;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.98

D;D;.

Vest4

0.52

MutPred

0.52

Loss of ubiquitination at K44 (P = 0.048);Loss of ubiquitination at K44 (P = 0.048);Loss of ubiquitination at K44 (P = 0.048);

MVP

0.26

MPC

1.1

ClinPred

0.64

GERP RS

4.3

PromoterAI

0.048

Neutral

(source)

Varity_R

0.79

gMVP

0.72

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over