X-8170145-G-C

Variant names:

• chrX-8170145-G-C
• rs772176238
• NM_016378.3:c.307C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016378.3(VCX2):​c.307C>G​(p.Pro103Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.0000029 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

Genes affected

VCX2 (HGNC:18158): (variable charge X-linked 2) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes that are expressed exclusively in male germ cells. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. This gene contains two copies of a 30 nt tandem repeat. Deletion of a nearby member of this family was implicated in cognitive disability. [provided by RefSeq, Feb 2015]

ENSG00000285679 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14621097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3	c.307C>G	p.Pro103Ala	missense_variant	Exon 3 of 3	ENST00000317103.5	NP_057462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX2	ENST00000317103.5	c.307C>G	p.Pro103Ala	missense_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4
ENSG00000285679	ENST00000649338.1	n.263-58190G>C		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1	n.972-58190G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000174 AC: 1 AN: 57321 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6577

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000315

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000289 AC: 3 AN: 1037712 Hom.: 0 Cov.: 29 AF XY: 0.00000631 AC XY: 2 AN XY: 316856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000376

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000174 AC: 1 AN: 57321 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6577

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000315

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.56
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.031
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		0.88	P
Vest4		0.13
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.10
MPC		0.0092
ClinPred		0.58	D
GERP RS		0.046
Varity_R		0.28
gMVP		0.0019

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: rs772176238; hg19: chrX-8138186;