X-6533750-C-G

Variant names:

• chrX-6533750-C-G
• rs74393938
• NM_016379.4:c.556G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016379.4(VCX3A):​c.556G>C​(p.Val186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 16)
• Consequence: VCX3A NM_016379.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05468139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4	c.556G>C	p.Val186Leu	missense_variant	Exon 3 of 3	ENST00000381089.7	NP_057463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7	c.556G>C	p.Val186Leu	missense_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3
VCX3A	ENST00000398729.1	c.496G>C	p.Val166Leu	missense_variant	Exon 4 of 4	5		ENSP00000381713.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.78
DEOGEN2	Benign	0.0018	T;.;.
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.20	N;.;N
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D;.;T
Sift4G	Benign	0.29	.;T;T
Polyphen		0.86	P;.;.
Vest4		0.054
MutPred		0.23		Gain of helix (P = 0.132);.;.;
MVP		0.043
MPC		0.26
ClinPred		0.12	T
GERP RS		0.46
Varity_R		0.20
gMVP		0.0077

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

Other links and lift over

dbSNP: rs74393938; hg19: chrX-6451791;