Variant X-8465919-G-A 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.277G>A(p.Glu93Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 0 hem., cov: 13)

Exomes 𝑓: 0.00034 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

VCX3B
NM_001001888.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.72

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=0.06418398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3B	NM_001001888.4 linkuse as main transcript	c.277G>A	p.Glu93Lys	missense_variant	3/3	ENST00000381032.6	NP_001001888.3	Q9H321-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3B	ENST00000381032.6 linkuse as main transcript	c.277G>A	p.Glu93Lys	missense_variant	3/3	5	NM_001001888.4	ENSP00000370420.1		Q9H321-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

87873

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

16537

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000708

Gnomad FIN

AF:

0.000289

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000319

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000338

AC:

307

AN:

909182

Hom.:

Cov.:

AF XY:

0.00000383

AC XY:

AN XY:

261386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000631

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000485

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.000179

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000182

AC:

AN:

87873

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

16537

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000708

Gnomad4 FIN

AF:

0.000289

Gnomad4 NFE

AF:

0.000319

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000296

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 26, 2024

The c.277G>A (p.E93K) alteration is located in exon 3 (coding exon 2) of the VCX3B gene. This alteration results from a G to A substitution at nucleotide position 277, causing the glutamic acid (E) at amino acid position 93 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0020

.;T;.;.

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.064

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.83

N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.062

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.94

.;P;.;.

Vest4

0.096

MutPred

0.30

Gain of methylation at E93 (P = 0.0011);Gain of methylation at E93 (P = 0.0011);Gain of methylation at E93 (P = 0.0011);Gain of methylation at E93 (P = 0.0011);

MVP

0.14

MPC

1.0

ClinPred

0.64

GERP RS

0.49

Varity_R

0.11

gMVP

0.016

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