Variant X-6533737-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000381089(VCX3A):c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 955,576 control chromosomes in the GnomAD database, including 111 homozygotes. There are 1,551 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 4 hom., 5 hem., cov: 9)

Exomes 𝑓: 0.0052 ( 107 hom. 1546 hem. )

Consequence

VCX3A
ENST00000381089 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.77

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042508543).

BP6

Variant X-6533737-C-T is Benign according to our data. Variant chrX-6533737-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058916.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3A	NM_016379.4 linkuse as main transcript	c.*8G>A		3_prime_UTR_variant	3/3	ENST00000381089.7	NP_057463.2	Q9NNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089 linkuse as main transcript	c.*8G>A		3_prime_UTR_variant	3/3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 linkuse as main transcript	c.*8G>A		downstream_gene_variant		5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

846

AN:

46922

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

AN XY:

13108

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.0128

Gnomad EAS

AF:

0.00832

Gnomad SAS

AF:

0.00771

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.00109

AC:

188

AN:

172626

Hom.:

AF XY:

0.00100

AC XY:

AN XY:

62702

show subpopulations

Gnomad AFR exome

AF:

0.00348

Gnomad AMR exome

AF:

0.000719

Gnomad ASJ exome

AF:

0.000839

Gnomad EAS exome

AF:

0.00268

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.000574

Gnomad NFE exome

AF:

0.000604

Gnomad OTH exome

AF:

0.000938

GnomAD4 exome

AF:

0.00518

AC:

4709

AN:

908674

Hom.:

107

Cov.:

AF XY:

0.00533

AC XY:

1546

AN XY:

289834

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.00469

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.00703

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.0180

AC:

844

AN:

46902

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

AN XY:

13120

show subpopulations

Gnomad4 AFR

AF:

0.0585

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.0128

Gnomad4 EAS

AF:

0.00833

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.00497

Hom.:

ExAC

AF:

0.00213

AC:

254

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VCX3A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.69

DANN

Benign

0.51

FATHMM_MKL

Benign

0.00042

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0043

MutationTaster

Benign

1.0

Sift4G

Benign

0.45

Vest4

0.15

MVP

0.082

ClinPred

0.0042

GERP RS

-0.22

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