chrX-8465781-A-G

Position:

chrX-8465781-A-G

Variant summary

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

The NM_001001888.4(VCX3B):c.139A>G(p.Arg47Gly) 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 0.00022 ( 0 hom., 0 hem., cov: 11)

Exomes 𝑓: 0.00020 ( 0 hom. 5 hem. )

Failed GnomAD Quality Control

Consequence

VCX3B
NM_001001888.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006706625).

BP6

Variant X-8465781-A-G is Benign according to our data. Variant chrX-8465781-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3331978.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3B	NM_001001888.4 linkuse as main transcript	c.139A>G	p.Arg47Gly	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.139A>G	p.Arg47Gly	missense_variant	3/3	5	NM_001001888.4	ENSP00000370420	P1	Q9H321-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

73784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11968

FAILED QC

Gnomad AFR

AF:

0.000476

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000314

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:

0.0000843

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000269

AC:

AN:

40913

Hom.:

AF XY:

0.00

AC XY:

AN XY:

13245

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000350

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000203

AC:

175

AN:

863417

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

240703

show subpopulations

Gnomad4 AFR exome

AF:

0.000177

Gnomad4 AMR exome

AF:

0.0000644

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000240

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.0000277

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.000342

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000217

AC:

AN:

73803

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11997

show subpopulations

Gnomad4 AFR

AF:

0.000475

Gnomad4 AMR

AF:

0.000313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000843

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.000385

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.5

DANN

Benign

0.26

DEOGEN2

Benign

0.0022

.;T;.;.

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.43

T;T;T;T

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.14

.;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.64

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.098

MutPred

0.30

Loss of methylation at R47 (P = 0.0268);Loss of methylation at R47 (P = 0.0268);Loss of methylation at R47 (P = 0.0268);Loss of methylation at R47 (P = 0.0268);

MVP

0.040

MPC

1.2

ClinPred

0.0042

GERP RS

-0.76

Varity_R

0.052

gMVP

0.0072

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