21-32515173-A-G

Position:

chr21-32515173-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_058187.5(EVA1C):c.1309A>G(p.Met437Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,592,162 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 6 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.195

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037037432).

BP6

Variant 21-32515173-A-G is Benign according to our data. Variant chr21-32515173-A-G is described in ClinVar as [Benign]. Clinvar id is 777058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00493 (751/152294) while in subpopulation AFR AF= 0.0171 (711/41560). AF 95% confidence interval is 0.0161. There are 6 homozygotes in gnomad4. There are 380 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVA1C	NM_058187.5 link	c.1309A>G	p.Met437Val	missense_variant	8/8	ENST00000300255.7	NP_478067.2	P58658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7 link	c.1309A>G	p.Met437Val	missense_variant	8/8	1	NM_058187.5	ENSP00000300255.2		P58658-1

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

752

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00145

AC:

347

AN:

239766

Hom.:

AF XY:

0.00109

AC XY:

141

AN XY:

129156

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.000977

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000763

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

AF:

0.000556

AC:

801

AN:

1439868

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

374

AN XY:

712542

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.000789

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000128

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00493

AC:

751

AN:

152294

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00587

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00166

AC:

201

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0064

T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.12

MVP

0.21

MPC

0.30

ClinPred

0.0024

GERP RS

-3.3

Varity_R

0.067

gMVP

0.39

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