chrX-8170119-T-G

Variant names:

• chrX-8170119-T-G
• rs1058238
• NM_016378.3:c.333A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016378.3(VCX2):​c.333A>C​(p.Glu111Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. E111G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 0.0000021 (1 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 7 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07455167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016378.3. 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
	VCX2	NM_016378.3	MANE Select	c.333A>C	p.Glu111Asp	missense	Exon 3 of 3	NP_057462.2	Q9H322

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX2	ENST00000317103.5	TSL:1 MANE Select	c.333A>C	p.Glu111Asp	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58216T>G		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58216T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000213 AC: 2 AN: 936981 Hom.: 1 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 330623

African (AFR) AF: 0.00 AC: 0 AN: 22708

American (AMR) AF: 0.00 AC: 0 AN: 30851

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17709

East Asian (EAS) AF: 0.00 AC: 0 AN: 28865

South Asian (SAS) AF: 0.00 AC: 0 AN: 49939

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37817

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2839

European-Non Finnish (NFE) AF: 0.00000283 AC: 2 AN: 705634

Other (OTH) AF: 0.00 AC: 0 AN: 40619

GnomAD4 genome Cov.: 10

Alfa AF: 0.00 Hom.: 4612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.73
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.82
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.068
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.050	T
Polyphen		0.39	B
Vest4		0.076
MutPred		0.13		Gain of helix (P = 0.0425)
MVP		0.048
MPC		0.0092
ClinPred		0.17	T
GERP RS		-0.093
Varity_R		0.26
gMVP		0.0024
Mutation Taster		=99/1	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: rs1058238; hg19: chrX-8138160;