Variant X-6533845-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016379.4(VCX3A):c.461T>C(p.Leu154Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 0 hem., cov: 16)

Exomes 𝑓: 0.000011 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.243

Variant links:

Genes affected

VCX3A (HGNC:18159): (variable charge X-linked 3A) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes, and all are expressed exclusively in male germ cells. The X-linked members are clustered on chromosome Xp22 and Y-linked members are two identical copies of the gene within a palindromic region on Yq11. The family members share a high degree of sequence identity, with the exception that a 30-bp unit is tandemly repeated in X-linked members but occurs only once in Y-linked members. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. This gene contains 8 repeats of the 30-bp unit. [provided by RefSeq, Jul 2008]

VCX3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009257764).

BP6

Variant X-6533845-A-G is Benign according to our data. Variant chrX-6533845-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 218737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-6533845-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3A	NM_016379.4 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/3	ENST00000381089.7	NP_057463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089.7 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/3	1	NM_016379.4	ENSP00000370479	P2
VCX3A	ENST00000398729.1 linkuse as main transcript	c.401T>C	p.Leu134Pro	missense_variant	4/4	5		ENSP00000381713	A2

Frequencies

GnomAD3 genomes

AF:

0.000229

AC:

AN:

87305

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20045

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000460

Gnomad EAS

AF:

0.00142

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000447

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

148729

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54725

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000185

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000110

AC:

AN:

998766

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

322692

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.00

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:

0.00000387

Gnomad4 OTH exome

AF:

0.0000481

GnomAD4 genome

AF:

0.000229

AC:

AN:

87314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20072

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000460

Gnomad4 EAS

AF:

0.00142

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000447

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000292

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jul 21, 2015

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.019

T;.

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.00086

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.2

D;N

REVEL

Benign

0.0090

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.17

T;T

Polyphen

0.0060

B;.

Vest4

0.058

MVP

0.043

MPC

0.43

ClinPred

0.031

GERP RS

0.51

Varity_R

0.49

gMVP

0.0025

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