Genetic Variant VCX3A:p.Val186Met (chrX-6533750-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016379.4(VCX3A):c.556G>A(p.Val186Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., 0 hem., cov: 16)

Exomes 𝑓: 0.0014 ( 3 hom. 75 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.735

Variant links:

Genes affected

VCX3A (HGNC:18159): (variable charge X-linked 3A) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes, and all are expressed exclusively in male germ cells. The X-linked members are clustered on chromosome Xp22 and Y-linked members are two identical copies of the gene within a palindromic region on Yq11. The family members share a high degree of sequence identity, with the exception that a 30-bp unit is tandemly repeated in X-linked members but occurs only once in Y-linked members. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. This gene contains 8 repeats of the 30-bp unit. [provided by RefSeq, Jul 2008]

VCX3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052250326).

BP6

Variant X-6533750-C-T is Benign according to our data. Variant chrX-6533750-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770511.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4 link	c.556G>A	p.Val186Met	missense_variant	Exon 3 of 3	ENST00000381089.7	NP_057463.2	Q9NNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7 link	c.556G>A	p.Val186Met	missense_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 link	c.496G>A	p.Val166Met	missense_variant	Exon 4 of 4	5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.00299

AC:

241

AN:

80721

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22037

show subpopulations

Gnomad AFR

AF:

0.00349

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00295

Gnomad EAS

AF:

0.000300

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.00710

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.00559

GnomAD3 exomes

AF:

0.000177

AC:

AN:

163904

Hom.:

AF XY:

0.0000512

AC XY:

AN XY:

58600

show subpopulations

Gnomad AFR exome

AF:

0.000175

Gnomad AMR exome

AF:

0.000155

Gnomad ASJ exome

AF:

0.000480

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00137

AC:

1199

AN:

878086

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

AN XY:

299974

show subpopulations

Gnomad4 AFR exome

AF:

0.000796

Gnomad4 AMR exome

AF:

0.000758

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.00172

Gnomad4 FIN exome

AF:

0.00326

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.00221

GnomAD4 genome

AF:

0.00298

AC:

241

AN:

80753

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22079

show subpopulations

Gnomad4 AFR

AF:

0.00348

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00295

Gnomad4 EAS

AF:

0.000301

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.00710

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.00549

Alfa

AF:

0.0188

Hom.:

ExAC

AF:

0.0310

AC:

3753

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VCX3A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

DANN

Benign

0.85

DEOGEN2

Benign

0.0018

T;.;.

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.43

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.14

N;.;N

REVEL

Benign

0.057

Sift

Pathogenic

0.0

D;.;T

Sift4G

Benign

0.10

.;T;T

Polyphen

0.98

D;.;.

Vest4

0.075

MPC

0.27

ClinPred

0.021

GERP RS

0.46

Varity_R

0.16

gMVP

0.011

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