Variant X-8170181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_016378.3(VCX2):c.271C>T(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 0 hem., cov: 7)

Exomes 𝑓: 0.0013 ( 0 hom. 464 hem. )

Failed GnomAD Quality Control

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -1.45

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033860594).

BP6

Variant X-8170181-G-A is Benign according to our data. Variant chrX-8170181-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206227.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-8170181-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX2	NM_016378.3 linkuse as main transcript	c.271C>T	p.Pro91Ser	missense_variant	3/3	ENST00000317103.5	NP_057462.2
LOC107985675	XR_001755783.2 linkuse as main transcript	n.1915-58154G>A		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.271C>T	p.Pro91Ser	missense_variant	3/3	1	NM_016378.3	ENSP00000321309	P1
	ENST00000659022.1 linkuse as main transcript	n.972-58154G>A		intron_variant, non_coding_transcript_variant
	ENST00000649338.1 linkuse as main transcript	n.263-58154G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000582

AC:

AN:

49854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5660

show subpopulations

Gnomad AFR

AF:

0.000335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000569

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:

0.000822

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000597

AC:

AN:

159026

Hom.:

AF XY:

0.000571

AC XY:

AN XY:

50828

show subpopulations

Gnomad AFR exome

AF:

0.000180

Gnomad AMR exome

AF:

0.0000793

Gnomad ASJ exome

AF:

0.000146

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00131

AC:

1422

AN:

1086696

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

464

AN XY:

355700

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.0000577

Gnomad4 ASJ exome

AF:

0.0000521

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000460

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.000768

GnomAD4 genome

AF:

0.000582

AC:

AN:

49864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5668

show subpopulations

Gnomad4 AFR

AF:

0.000334

Gnomad4 AMR

AF:

0.000569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000822

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

ESP6500AA

AF:

0.000264

AC:

ESP6500EA

AF:

0.000754

AC:

ExAC

AF:

0.000738

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.4

DANN

Benign

0.94

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.63

M_CAP

Benign

0.0017

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.042

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.036

Polyphen

0.94

Vest4

0.12

MVP

0.16

MPC

0.0091

ClinPred

0.073

GERP RS

0.046

Varity_R

0.18

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over