Variant X-8465760-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001888.4(VCX3B):c.118A>G(p.Lys40Glu) 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 0 hem., cov: 11)

Exomes 𝑓: 0.0013 ( 1 hom. 57 hem. )

Failed GnomAD Quality Control

Consequence

VCX3B
NM_001001888.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.438

Variant links:

Genes affected

VCX3B (HGNC:31838): (variable charge X-linked 3B) 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 the Y-linked members are two identical copies of the gene within a palindromic region on chromosome Yq11. The family members share a high degree of sequence identity, with the exception that a 30-nt 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. This family member, as represented by the reference genome allele, contains 14 copies of the 30-nt repeat unit. VCX/Y genes encode small and highly charged proteins containing putative bipartite nuclear localization signals. Although the exact function of this family member has yet to be determined, a role in mRNA stability regulation can be inferred from the ability of the highly similar family member, VCX-A, to inhibit mRNA decapping. A possible role in the regulation of ribosome assembly during spermatogenesis has also been suggested. [provided by RefSeq, Aug 2010]

VCX3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058926344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3B	NM_001001888.4 linkuse as main transcript	c.118A>G	p.Lys40Glu	missense_variant	3/3	ENST00000381032.6	NP_001001888.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3B	ENST00000381032.6 linkuse as main transcript	c.118A>G	p.Lys40Glu	missense_variant	3/3	5	NM_001001888.4	ENSP00000370420	P1	Q9H321-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

AN:

72413

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11993

show subpopulations

Gnomad AFR

AF:

0.000978

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00110

Gnomad ASJ

AF:

0.00170

Gnomad EAS

AF:

0.00103

Gnomad SAS

AF:

0.00355

Gnomad FIN

AF:

0.000864

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00106

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00129

AC:

1211

AN:

936883

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

265723

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00125

Gnomad4 EAS exome

AF:

0.00419

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000935

GnomAD4 genome

AF:

0.00116

AC:

AN:

72444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12032

show subpopulations

Gnomad4 AFR

AF:

0.000976

Gnomad4 AMR

AF:

0.00110

Gnomad4 ASJ

AF:

0.00170

Gnomad4 EAS

AF:

0.00104

Gnomad4 SAS

AF:

0.00358

Gnomad4 FIN

AF:

0.000864

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00104

Alfa

AF:

0.00100

Hom.:

ExAC

AF:

0.000501

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

Sep 28, 2021

The c.118A>G (p.K40E) alteration is located in exon 3 (coding exon 2) of the VCX3B gene. This alteration results from a A to G substitution at nucleotide position 118, causing the lysine (K) at amino acid position 40 to be replaced by a glutamic acid (E). 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

0.19

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.1

DANN

Benign

0.27

DEOGEN2

Benign

0.012

.;T;.;.

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.43

T;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.44

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.018

.;B;.;.

Vest4

0.10

MVP

0.13

MPC

1.3

ClinPred

0.0019

GERP RS

-0.76

Varity_R

0.065

gMVP

0.014

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