Variant X-6533801-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016379.4(VCX3A):c.505C>G(p.Gln169Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.00038 ( 0 hom. 52 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -1.99

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056487024).

BP6

Variant X-6533801-G-C is Benign according to our data. Variant chrX-6533801-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206081.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-6533801-G-C is described in Lovd as [Benign]. Variant chrX-6533801-G-C 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.505C>G	p.Gln169Glu	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.505C>G	p.Gln169Glu	missense_variant	3/3	1	NM_016379.4	ENSP00000370479	P2
VCX3A	ENST00000398729.1 linkuse as main transcript	c.445C>G	p.Gln149Glu	missense_variant	4/4	5		ENSP00000381713	A2

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

AN:

87417

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

21741

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000360

Gnomad ASJ

AF:

0.000912

Gnomad EAS

AF:

0.000733

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000613

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000380

AC:

384

AN:

1010445

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

333651

show subpopulations

Gnomad4 AFR exome

AF:

0.000260

Gnomad4 AMR exome

AF:

0.0000317

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000414

Gnomad4 SAS exome

AF:

0.000317

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.000335

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00105

AC:

AN:

87443

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

21775

show subpopulations

Gnomad4 AFR

AF:

0.00259

Gnomad4 AMR

AF:

0.000360

Gnomad4 ASJ

AF:

0.000912

Gnomad4 EAS

AF:

0.000736

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000613

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00641

Hom.:

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.00521

AC:

ExAC

AF:

0.00239

AC:

283

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.92

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.053

DANN

Benign

0.11

DEOGEN2

Benign

0.0013

T;.

FATHMM_MKL

Benign

0.00075

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.11

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.42

B;.

Vest4

0.072

MVP

0.043

MPC

0.29

ClinPred

0.069

GERP RS

-1.2

Varity_R

0.089

gMVP

0.00089

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