X-6533781-A-C

Variant names:

• chrX-6533781-A-C
• rs761292721
• NM_016379.4:c.525T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016379.4(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. 13/21 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 NM_016379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016379.4. 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
	VCX3A	NM_016379.4	MANE Select	c.525T>G	p.Ser175Arg	missense	Exon 3 of 3	NP_057463.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX3A	ENST00000381089.7	TSL:1 MANE Select	c.525T>G	p.Ser175Arg	missense	Exon 3 of 3	ENSP00000370479.3	Q9NNX9
	VCX3A	ENST00000898738.1		c.525T>G	p.Ser175Arg	missense	Exon 2 of 2	ENSP00000568797.1
	VCX3A	ENST00000398729.1	TSL:5	c.465T>G	p.Ser155Arg	missense	Exon 4 of 4	ENSP00000381713.1	E7ESE9

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.00064	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.028
Sift	Benign	0.041	D
Sift4G	Uncertain	0.019	D
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs761292721; hg19: chrX-6451822;