Variant X-7843963-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393662.1(VCX):c.568G>A(p.Val190Met) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., 2 hem., cov: 11)

Exomes 𝑓: 0.0058 ( 63 hom. 761 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

VCX (HGNC:12667): (variable charge X-linked) 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 10 repeats of the 30-bp unit. [provided by RefSeq, Jul 2008]

VCX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065913796).

BP6

Variant X-7843963-G-A is Benign according to our data. Variant chrX-7843963-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659919.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VCX	NM_001393662.1 linkuse as main transcript	c.568G>A	p.Val190Met	missense_variant	2/2	ENST00000688183.1	NP_001380591.1
VCX	NM_013452.3 linkuse as main transcript	c.568G>A	p.Val190Met	missense_variant	3/3		NP_038480.2
VCX	XM_011545490.4 linkuse as main transcript	c.538-30G>A		intron_variant			XP_011543792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX	ENST00000688183.1 linkuse as main transcript	c.568G>A	p.Val190Met	missense_variant	2/2		NM_001393662.1	ENSP00000509688	P1

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

301

AN:

71190

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

13324

show subpopulations

Gnomad AFR

AF:

0.000592

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00156

Gnomad ASJ

AF:

0.00772

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00607

Gnomad FIN

AF:

0.00704

Gnomad MID

AF:

0.00800

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.00341

GnomAD3 exomes

AF:

0.000855

AC:

151

AN:

176617

Hom.:

AF XY:

0.000593

AC XY:

AN XY:

64041

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.000223

Gnomad ASJ exome

AF:

0.000550

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000713

Gnomad FIN exome

AF:

0.00412

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00583

AC:

4131

AN:

708099

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

761

AN XY:

225989

show subpopulations

Gnomad4 AFR exome

AF:

0.000441

Gnomad4 AMR exome

AF:

0.00269

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000404

Gnomad4 SAS exome

AF:

0.00579

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00598

Gnomad4 OTH exome

AF:

0.00581

GnomAD4 genome

AF:

0.00421

AC:

300

AN:

71203

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

13349

show subpopulations

Gnomad4 AFR

AF:

0.000591

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00772

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00612

Gnomad4 FIN

AF:

0.00704

Gnomad4 NFE

AF:

0.00660

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00455

Hom.:

ExAC

AF:

0.00428

AC:

494

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

VCX: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.012

T;.

FATHMM_MKL

Benign

0.00026

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.26

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.11

Sift

Benign

0.14

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.96

D;.

Vest4

0.067

MVP

0.043

MPC

0.35

ClinPred

0.0089

Varity_R

0.11

gMVP

0.0032

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