Variant X-6533768-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016379.4(VCX3A):c.538A>G(p.Met180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., 8 hem., cov: 18)

Exomes 𝑓: 0.00083 ( 1 hom. 93 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.84

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050979555).

BP6

Variant X-6533768-T-C is Benign according to our data. Variant chrX-6533768-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659907.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3A	NM_016379.4 linkuse as main transcript	c.538A>G	p.Met180Val	missense_variant	3/3	ENST00000381089.7	NP_057463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7 linkuse as main transcript	c.538A>G	p.Met180Val	missense_variant	3/3	1	NM_016379.4	ENSP00000370479	P2
VCX3A	ENST00000398729.1 linkuse as main transcript	c.478A>G	p.Met160Val	missense_variant	4/4	5		ENSP00000381713	A2

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

321

AN:

99706

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

AN XY:

25718

show subpopulations

Gnomad AFR

AF:

0.000522

Gnomad AMI

AF:

0.0234

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000815

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000967

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00155

GnomAD3 exomes

AF:

0.000748

AC:

134

AN:

179027

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

66313

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.000593

Gnomad ASJ exome

AF:

0.000540

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000213

Gnomad FIN exome

AF:

0.000825

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000831

AC:

892

AN:

1073027

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

AN XY:

355485

show subpopulations

Gnomad4 AFR exome

AF:

0.000115

Gnomad4 AMR exome

AF:

0.000862

Gnomad4 ASJ exome

AF:

0.000208

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0000749

Gnomad4 FIN exome

AF:

0.000355

Gnomad4 NFE exome

AF:

0.000979

Gnomad4 OTH exome

AF:

0.000666

GnomAD4 genome

AF:

0.00322

AC:

321

AN:

99747

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

AN XY:

25761

show subpopulations

Gnomad4 AFR

AF:

0.000521

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000815

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000967

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00153

Alfa

AF:

0.00715

Hom.:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00997

AC:

ExAC

AF:

0.00234

AC:

282

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

VCX3A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.088

DANN

Benign

0.33

DEOGEN2

Benign

0.0037

T;.

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.00094

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.0060

Sift

Benign

1.0

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.047

B;.

Vest4

0.052

MVP

0.043

MPC

0.27

ClinPred

0.00089

Varity_R

0.087

gMVP

0.0046

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