Genetic Variant VCX2:p.Asp139Asn (chrX-8170037-C-T) – 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.415G>A(p.Asp139Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,188,341 control chromosomes in the GnomAD database, including 3 homozygotes. There are 139 hemizygotes 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 0.00023 ( 0 hom., 4 hem., cov: 13)

Exomes 𝑓: 0.00039 ( 3 hom. 135 hem. )

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

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=0.019512564).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3 link	c.415G>A	p.Asp139Asn	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.415G>A	p.Asp139Asn	missense_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4	Q9H322
ENSG00000285679	ENST00000649338.1 link	n.263-58298C>T		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1 link	n.972-58298C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000229

AC:

AN:

91839

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

17305

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:

0.00108

Gnomad SAS

AF:

0.000601

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000365

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000303

AC:

AN:

181495

Hom.:

AF XY:

0.000312

AC XY:

AN XY:

67415

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000795

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000498

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000391

AC:

429

AN:

1096478

Hom.:

Cov.:

AF XY:

0.000372

AC XY:

135

AN XY:

362828

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.0000757

Gnomad4 NFE exome

AF:

0.000461

Gnomad4 OTH exome

AF:

0.000522

GnomAD4 genome

AF:

0.000229

AC:

AN:

91863

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

17339

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00109

Gnomad4 SAS

AF:

0.000604

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000365

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000189

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000398

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.57

DANN

Benign

0.95

DEOGEN2

Benign

0.0012

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.34

M_CAP

Benign

0.0012

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.28

REVEL

Benign

0.070

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.030

Polyphen

0.98

Vest4

0.085

MVP

0.030

MPC

0.0091

ClinPred

0.047

GERP RS

0.19

Varity_R

0.090

gMVP

0.0017

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