X-8170052-C-T

Position:

chrX-8170052-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016378.3(VCX2):c.400G>A(p.Val134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,195,230 control chromosomes in the GnomAD database, including 2 homozygotes. There are 138 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., 10 hem., cov: 15)

Exomes 𝑓: 0.00035 ( 1 hom. 128 hem. )

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.12

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005207807).

BP6

Variant X-8170052-C-T is Benign according to our data. Variant chrX-8170052-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2411588.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-8170052-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX2	NM_016378.3 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	3/3	ENST00000317103.5	NP_057462.2
LOC107985675	XR_001755783.2 linkuse as main transcript	n.1915-58283C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
VCX2	ENST00000317103.5 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	3/3	1	NM_016378.3	ENSP00000321309	P1
	ENST00000659022.1 linkuse as main transcript	n.972-58283C>T		intron_variant, non_coding_transcript_variant
	ENST00000649338.1 linkuse as main transcript	n.263-58283C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

98724

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

22278

show subpopulations

Gnomad AFR

AF:

0.0000751

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000112

Gnomad ASJ

AF:

0.00892

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000184

Gnomad OTH

AF:

0.000777

GnomAD3 exomes

AF:

0.000688

AC:

125

AN:

181740

Hom.:

AF XY:

0.000724

AC XY:

AN XY:

67640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000361

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.000347

AC:

381

AN:

1096506

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

128

AN XY:

362854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000869

GnomAD4 genome

AF:

0.000355

AC:

AN:

98724

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

22278

show subpopulations

Gnomad4 AFR

AF:

0.0000751

Gnomad4 AMR

AF:

0.000112

Gnomad4 ASJ

AF:

0.00892

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000184

Gnomad4 OTH

AF:

0.000777

Alfa

AF:

0.000774

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000746

AC:

ExAC

AF:

0.000597

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.016

DANN

Benign

0.75

DEOGEN2

Benign

0.0012

FATHMM_MKL

Benign

0.00011

LIST_S2

Benign

0.30

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.28

REVEL

Benign

0.022

Sift

Benign

0.30

Sift4G

Benign

0.69

Polyphen

0.014

Vest4

0.035

MVP

0.014

MPC

0.0094

ClinPred

0.036

GERP RS

-0.093

Varity_R

0.093

gMVP

0.0011

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over