X-6533888-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016379.4(VCX3A):c.418G>A(p.Val140Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 0 hom., 0 hem., cov: 13)

Exomes 𝑓: 0.0015 ( 0 hom. 15 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.36

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0084787905).

BP6

Variant X-6533888-C-T is Benign according to our data. Variant chrX-6533888-C-T is described in ClinVar as [Benign]. Clinvar id is 218736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-6533888-C-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4 link	c.418G>A	p.Val140Met	missense_variant	Exon 3 of 3	ENST00000381089.7	NP_057463.2	Q9NNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7 link	c.418G>A	p.Val140Met	missense_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 link	c.358G>A	p.Val120Met	missense_variant, splice_region_variant	Exon 4 of 4	5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

462

AN:

66340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

14768

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00198

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00463

Gnomad EAS

AF:

0.00678

Gnomad SAS

AF:

0.00156

Gnomad FIN

AF:

0.00338

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00549

Gnomad OTH

AF:

0.0111

GnomAD3 exomes

AF:

0.0432

AC:

1218

AN:

28216

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

11360

show subpopulations

Gnomad AFR exome

AF:

0.0898

Gnomad AMR exome

AF:

0.00665

Gnomad ASJ exome

AF:

0.0233

Gnomad EAS exome

AF:

0.0300

Gnomad SAS exome

AF:

0.00722

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.0359

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00154

AC:

598

AN:

388549

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

149135

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.00178

Gnomad4 SAS exome

AF:

0.000983

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00700

AC:

464

AN:

66319

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

14779

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.00463

Gnomad4 EAS

AF:

0.00680

Gnomad4 SAS

AF:

0.00158

Gnomad4 FIN

AF:

0.00338

Gnomad4 NFE

AF:

0.00549

Gnomad4 OTH

AF:

0.0111

ExAC

AF:

0.0240

AC:

950

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Mar 06, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.66

DANN

Benign

0.62

DEOGEN2

Benign

0.0069

T;.

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

N;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.014

Sift

Benign

0.098

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.28

B;.

Vest4

0.047

MPC

0.27

ClinPred

0.0020

Varity_R

0.19

gMVP

0.0044

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