X-7843963-G-T

Variant names:

• chrX-7843963-G-T
• rs201876650
• NM_001393662.1:c.568G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393662.1(VCX):​c.568G>T​(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: 0.0000056 (1 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX NM_001393662.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04647696).

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>T	p.Val190Leu	missense	Exon 2 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.568G>T	p.Val190Leu	missense	Exon 3 of 3	NP_038480.2	Q9H320

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD2 exomes AF: 0.0000170 AC: 3 AN: 176617 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000559 AC: 4 AN: 716056 Hom.: 1 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 229468

African (AFR) AF: 0.00 AC: 0 AN: 15891

American (AMR) AF: 0.00 AC: 0 AN: 21650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12816

East Asian (EAS) AF: 0.0000806 AC: 2 AN: 24828

South Asian (SAS) AF: 0.00 AC: 0 AN: 40761

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2258

European-Non Finnish (NFE) AF: 0.00000375 AC: 2 AN: 533253

Other (OTH) AF: 0.00 AC: 0 AN: 31623

GnomAD4 genome Cov.: 11

ExAC AF: 0.0000346 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.8
DANN	Benign	0.39
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.11	N
PhyloP100		-1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.024
Sift	Benign	0.31	T
Sift4G	Benign	0.37	T
Polyphen		0.0060	B
Vest4		0.060
MutPred		0.20		Gain of glycosylation at P193 (P = 0.1309)
MVP		0.043
MPC		0.35
ClinPred		0.017	T
Varity_R		0.11
gMVP		0.0023
Mutation Taster		=100/0	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: rs201876650; hg19: chrX-7812004;