dbSNP rs139229818: VCX2:p.Glu97Gln (chrX-8170163-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016378.3(VCX2):c.289G>C(p.Glu97Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,136,262 control chromosomes in the GnomAD database, including 1 homozygotes. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0022 ( 1 hom., 1 hem., cov: 8)

Exomes 𝑓: 0.00015 ( 0 hom. 21 hem. )

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.775

Variant links:

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]

VCX2 links:

ENSG00000285679 (HGNC:):

ENSG00000285679 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071898103).

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3 link	c.289G>C	p.Glu97Gln	missense_variant	Exon 3 of 3	ENST00000317103.5	NP_057462.2	Q9H322

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VCX2	ENST00000317103.5 link	c.289G>C	p.Glu97Gln	missense_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4	Q9H322
ENSG00000285679	ENST00000649338.1 link	n.263-58172C>G		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1 link	n.972-58172C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

119

AN:

54843

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

6255

show subpopulations

Gnomad AFR

AF:

0.00862

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000512

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:

0.00496

GnomAD3 exomes

AF:

0.000487

AC:

AN:

154095

Hom.:

AF XY:

0.000388

AC XY:

AN XY:

46389

show subpopulations

Gnomad AFR exome

AF:

0.00586

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000603

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

166

AN:

1081432

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

AN XY:

351252

show subpopulations

Gnomad4 AFR exome

AF:

0.00429

Gnomad4 AMR exome

AF:

0.000352

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:

0.0000276

Gnomad4 OTH exome

AF:

0.000462

GnomAD4 genome

AF:

0.00217

AC:

119

AN:

54830

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

6262

show subpopulations

Gnomad4 AFR

AF:

0.00862

Gnomad4 AMR

AF:

0.000513

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00487

Alfa

AF:

0.000193

Hom.:

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000935

AC:

111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.51

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.3

REVEL

Benign

0.067

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.90

Vest4

0.30

MVP

0.14

MPC

0.0091

ClinPred

0.067

GERP RS

0.046

Varity_R

0.46

gMVP

0.0034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over