X-8170178-C-T

Variant names:

• chrX-8170178-C-T
• rs759918077
• NM_016378.3:c.274G>A

Variant summary

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

The NM_016378.3(VCX2):​c.274G>A​(p.Glu92Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E92Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 7)
  • Exomes 𝑓: 0.000066 (0 hom. 20 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 0 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=0.11540803).

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.274G>A	p.Glu92Lys	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.274G>A	p.Glu92Lys	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58157C>T		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58157C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 50858 Hom.: 0 Cov.: 7

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000631 AC: 1 AN: 158357 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000147

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000662 AC: 72 AN: 1087535 Hom.: 0 Cov.: 32 AF XY: 0.0000562 AC XY: 20 AN XY: 356087

African (AFR) AF: 0.00 AC: 0 AN: 26182

American (AMR) AF: 0.00 AC: 0 AN: 34649

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19221

East Asian (EAS) AF: 0.00 AC: 0 AN: 29960

South Asian (SAS) AF: 0.00 AC: 0 AN: 53603

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39163

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2874

European-Non Finnish (NFE) AF: 0.0000789 AC: 66 AN: 836255

Other (OTH) AF: 0.000131 AC: 6 AN: 45628

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 50858 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 5800

African (AFR) AF: 0.00 AC: 0 AN: 12196

American (AMR) AF: 0.00 AC: 0 AN: 3603

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1552

East Asian (EAS) AF: 0.00 AC: 0 AN: 1121

South Asian (SAS) AF: 0.00 AC: 0 AN: 701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2235

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 61

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28481

Other (OTH) AF: 0.00 AC: 0 AN: 561

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000839 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.0043	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.092
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.022	D
Polyphen		0.59	P
Vest4		0.21
MutPred		0.13		Gain of ubiquitination at E92 (P = 9e-04)
MVP		0.16
MPC		0.0090
ClinPred		0.091	T
GERP RS		0.046
Varity_R		0.23
gMVP		0.0022
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: rs759918077; hg19: chrX-8138219;