NM_058187.5:c.1054C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_058187.5(EVA1C):c.1054C>T(p.Arg352Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,614,052 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R352H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 9 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.670

Publications

4 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:

TCP10L (HGNC:11657): (t-complex 10 like) Enables several functions, including identical protein binding activity; protein self-association; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCP10L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003971368).

BP6

Variant 21-32514918-C-T is Benign according to our data. Variant chr21-32514918-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652600.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5 link	c.1054C>T	p.Arg352Cys	missense_variant	Exon 8 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.1054C>T	p.Arg352Cys	missense_variant	Exon 8 of 8	1	NM_058187.5	ENSP00000300255.2		P58658-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00686

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00117

AC:

294

AN:

250928

AF XY:

0.00158

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000627

AC:

917

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

646

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00778

AC:

671

AN:

86252

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00557

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000140

AC:

156

AN:

1112008

Other (OTH)

AF:

0.000844

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000342

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41528

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00644

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EVA1C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.071

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.5

M;.;.

PhyloP100

0.67

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.16

MVP

0.35

MPC

0.62

ClinPred

0.033

GERP RS

2.6

Varity_R

0.27

gMVP

0.20

Mutation Taster

=98/2

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

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NM_058187.5:c.1054C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over