chrX-7843210-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• 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: 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=0.08935419).

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.7C>G	p.Pro3Ala	missense	Exon 1 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.7C>G	p.Pro3Ala	missense	Exon 2 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.7C>G	p.Pro3Ala	missense	Exon 1 of 2	ENSP00000509688.1	Q9H320
	VCX	ENST00000381059.7	TSL:1	c.7C>G	p.Pro3Ala	missense	Exon 2 of 3	ENSP00000370447.3	Q9H320
	VCX	ENST00000341408.6	TSL:5	c.7C>G	p.Pro3Ala	missense	Exon 1 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.090
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.14
MutPred		0.27		Loss of glycosylation at P3 (P = 0.0221)
MVP		0.043
MPC		0.34
ClinPred		0.11	T
GERP RS		0.17
PromoterAI		0.072	Neutral
Varity_R		0.12
gMVP		0.0031
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: rs146106202; hg19: chrX-7811251;