Genetic Variant VCX2:p.Ser137Thr (chrX-8170042-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016378.3(VCX2):c.410G>C(p.Ser137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,195,162 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.000010 ( 0 hom., 0 hem., cov: 15)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.525

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08539292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3 link	c.410G>C	p.Ser137Thr	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.410G>C	p.Ser137Thr	missense_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4	Q9H322
ENSG00000285679	ENST00000649338.1 link	n.263-58293C>G		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1 link	n.972-58293C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000101

AC:

AN:

98589

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22159

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000334

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

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181659

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67567

show subpopulations

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 SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1096545

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362865

show subpopulations

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:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000101

AC:

AN:

98617

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22197

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000335

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.0

DANN

Benign

0.76

DEOGEN2

Benign

0.0035

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.20

M_CAP

Benign

0.0012

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

REVEL

Benign

0.076

Sift

Benign

0.070

Sift4G

Benign

0.17

Polyphen

0.22

Vest4

0.074

MutPred

0.068

Loss of glycosylation at S137 (P = 0.0402);

MVP

0.030

MPC

0.0092

ClinPred

0.088

GERP RS

0.19

Varity_R

0.21

gMVP

0.0021

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