Genetic Variant VCX:p.Val190Leu (chrX-7843963-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393662.1(VCX):c.568G>C(p.Val190Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V190M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 11)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068594486).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393662.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX	NM_001393662.1	MANE Select	c.568G>C	p.Val190Leu	missense	Exon 2 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.568G>C	p.Val190Leu	missense	Exon 3 of 3	NP_038480.2	Q9H320

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCX	ENST00000688183.1	MANE Select	c.568G>C	p.Val190Leu	missense	Exon 2 of 2	ENSP00000509688.1	Q9H320
VCX	ENST00000381059.7	TSL:1	c.568G>C	p.Val190Leu	missense	Exon 3 of 3	ENSP00000370447.3	Q9H320
VCX	ENST00000341408.6	TSL:5	c.508G>C	p.Val170Leu	missense	Exon 3 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

716052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

229466

African (AFR)

AF:

0.00

AC:

AN:

15891

American (AMR)

AF:

0.00

AC:

AN:

21650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12816

East Asian (EAS)

AF:

0.00

AC:

AN:

24831

South Asian (SAS)

AF:

0.00

AC:

AN:

40762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

533245

Other (OTH)

AF:

0.00

AC:

AN:

31623

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000865

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

7.0

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0053

FATHMM_MKL

Benign

0.00066

LIST_S2

Benign

0.39

M_CAP

Benign

0.0029

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.11

PhyloP100

-1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.62

REVEL

Benign

0.024

Sift

Benign

0.31

Sift4G

Benign

0.37

Polyphen

0.0060

Vest4

0.060

MutPred

0.20

Gain of glycosylation at P193 (P = 0.1309)

MVP

0.043

MPC

0.35

ClinPred

0.039

Varity_R

0.11

gMVP

0.0023

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over