X-6533781-A-C

Position:

• chrX-6533781-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000381089.7(VCX3A):​c.525T>G​(p.Ser175Arg) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: VCX3A ENST00000381089.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09575352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3A	NM_016379.4	c.525T>G	p.Ser175Arg	missense_variant	3/3	ENST00000381089.7	NP_057463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7	c.525T>G	p.Ser175Arg	missense_variant	3/3	1	NM_016379.4	ENSP00000370479.3
VCX3A	ENST00000398729.1	c.465T>G	p.Ser155Arg	missense_variant	4/4	5		ENSP00000381713.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.525T>G (p.S175R) alteration is located in exon 3 (coding exon 2) of the VCX3A gene. This alteration results from a T to G substitution at nucleotide position 525, causing the serine (S) at amino acid position 175 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.56
DEOGEN2	Benign	0.0091	T;.
FATHMM_MKL	Benign	0.00073	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.00064	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.028
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.019	D;T
Polyphen		0.010	B;.
Vest4		0.075
MutPred		0.23		Loss of phosphorylation at S175 (P = 0.0017);.;
MVP		0.043
MPC		0.30
ClinPred		0.039	T
GERP RS		-1.2
Varity_R		0.39
gMVP		0.0096

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-6451822;