rs146106202

Variant names:

• chrX-7843210-C-G
• rs146106202
• NM_001393662.1:c.7C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-7843210-C-G
• chrX-7843210-C-T

Variant summary

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

The NM_001393662.1(VCX):​c.7C>G​(p.Pro3Ala) 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. 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. P3S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 19)
• Consequence: VCX NM_001393662.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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

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=0.08935419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX	NM_001393662.1	c.7C>G	p.Pro3Ala	missense_variant	Exon 1 of 2	ENST00000688183.1	NP_001380591.1
VCX	NM_013452.3	c.7C>G	p.Pro3Ala	missense_variant	Exon 2 of 3		NP_038480.2
VCX	XM_011545490.4	c.7C>G	p.Pro3Ala	missense_variant	Exon 1 of 3		XP_011543792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX	ENST00000688183.1	c.7C>G	p.Pro3Ala	missense_variant	Exon 1 of 2		NM_001393662.1	ENSP00000509688.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 19

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.013	T;.;.
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.64	N;.;N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.14
MutPred		0.27		Loss of glycosylation at P3 (P = 0.0221);Loss of glycosylation at P3 (P = 0.0221);Loss of glycosylation at P3 (P = 0.0221);
MVP		0.043
MPC		0.34
ClinPred		0.11	T
GERP RS		0.17
Varity_R		0.12
gMVP		0.0031

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: rs146106202; hg19: chrX-7811251;