chrX-8170102-T-C

Position:

• chrX-8170102-T-C

Variant summary

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

The NM_016378.3(VCX2):​c.350A>G​(p.Glu117Gly) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 14)
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0580

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 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=0.09459895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX2	NM_016378.3	c.350A>G	p.Glu117Gly	missense_variant	3/3	ENST00000317103.5	NP_057462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX2	ENST00000317103.5	c.350A>G	p.Glu117Gly	missense_variant	3/3	1	NM_016378.3	ENSP00000321309.4
ENSG00000285679	ENST00000649338.1	n.263-58233T>C		intron_variant
ENSG00000285679	ENST00000659022.1	n.972-58233T>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.350A>G (p.E117G) alteration is located in exon 3 (coding exon 2) of the VCX2 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the glutamic acid (E) at amino acid position 117 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.45
DEOGEN2	Benign	0.0029	T
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.11
Sift	Benign	0.44	T
Sift4G	Benign	0.46	T
Polyphen		0.77	P
Vest4		0.18
MutPred		0.098		Loss of solvent accessibility (P = 0.0387);
MVP		0.12
MPC		0.0089
ClinPred		0.19	T
Varity_R		0.055
gMVP		0.0065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-8138143;