Variant X-6533795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016379.4(VCX3A):c.511G>A(p.Glu171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.00014 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07378614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3A	NM_016379.4 linkuse as main transcript	c.511G>A	p.Glu171Lys	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.511G>A	p.Glu171Lys	missense_variant	3/3	1	NM_016379.4	ENSP00000370479	P2
VCX3A	ENST00000398729.1 linkuse as main transcript	c.451G>A	p.Glu151Lys	missense_variant	4/4	5		ENSP00000381713	A2

Frequencies

GnomAD3 genomes

AF:

0.000260

AC:

AN:

100109

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

26479

show subpopulations

Gnomad AFR

AF:

0.000109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000478

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

180511

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66633

show subpopulations

Gnomad AFR exome

AF:

0.0000770

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000875

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000137

AC:

141

AN:

1026504

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

340284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.0000940

GnomAD4 genome

AF:

0.000260

AC:

AN:

100139

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

26525

show subpopulations

Gnomad4 AFR

AF:

0.000109

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000478

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000422

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000292

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.511G>A (p.E171K) alteration is located in exon 3 (coding exon 2) of the VCX3A gene. This alteration results from a G to A substitution at nucleotide position 511, causing the glutamic acid (E) at amino acid position 171 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

DANN

Benign

0.92

DEOGEN2

Benign

0.0083

T;.

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.016

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.0030

B;.

Vest4

0.081

MVP

0.043

MPC

0.30

ClinPred

0.020

GERP RS

-1.2

Varity_R

0.15

gMVP

0.019

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