Variant X-7843943-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001393662.1(VCX):c.548C>T(p.Pro183Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., 0 hem., cov: 11)

Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -1.37

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 Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09929541).

BP6

Variant X-7843943-C-T is Benign according to our data. Variant chrX-7843943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1206112.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-7843943-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VCX	NM_001393662.1 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	2/2	ENST00000688183.1	NP_001380591.1
VCX	NM_013452.3 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	3/3		NP_038480.2
VCX	XM_011545490.4 linkuse as main transcript	c.537+11C>T		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.548C>T	p.Pro183Leu	missense_variant	2/2		NM_001393662.1	ENSP00000509688	P1

Frequencies

GnomAD3 genomes

AF:

0.0000412

AC:

AN:

72848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

13820

show subpopulations

Gnomad AFR

AF:

0.000149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

172854

Hom.:

AF XY:

0.00

AC XY:

AN XY:

60174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000145

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000261

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000152

AC:

AN:

725585

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

233335

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000775

Gnomad4 EAS exome

AF:

0.0000399

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000412

AC:

AN:

72848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

13820

show subpopulations

Gnomad4 AFR

AF:

0.000149

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.019

T;.

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.039

Sift

Pathogenic

0.0

D;T

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.0060

B;.

Vest4

0.076

MVP

0.043

MPC

0.36

ClinPred

0.10

Varity_R

0.26

gMVP

0.0071

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