dbSNP rs77413590: VCX3A:c.*9C>G (chrX-6533736-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_016379.4(VCX3A):c.*9C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 966,755 control chromosomes in the GnomAD database, including 110 homozygotes. There are 1,554 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 0.017 ( 3 hom., 4 hem., cov: 9)

Exomes 𝑓: 0.0051 ( 107 hom. 1550 hem. )

Consequence

VCX3A
NM_016379.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.634

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=0.0065132678).

BP6

Variant X-6533736-G-C is Benign according to our data. Variant chrX-6533736-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3060492.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4 link	c.*9C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000381089.7	NP_057463.2	Q9NNX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX3A	ENST00000381089 link	c.*9C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 link	c.*9C>G		downstream_gene_variant		5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

839

AN:

47931

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

AN XY:

13299

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00820

Gnomad SAS

AF:

0.00758

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0252

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.00106

AC:

184

AN:

172838

Hom.:

AF XY:

0.00100

AC XY:

AN XY:

62736

show subpopulations

Gnomad AFR exome

AF:

0.00347

Gnomad AMR exome

AF:

0.000718

Gnomad ASJ exome

AF:

0.000840

Gnomad EAS exome

AF:

0.00250

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.000574

Gnomad NFE exome

AF:

0.000578

Gnomad OTH exome

AF:

0.000937

GnomAD4 exome

AF:

0.00510

AC:

4686

AN:

918845

Hom.:

107

Cov.:

AF XY:

0.00529

AC XY:

1550

AN XY:

293137

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.00698

Gnomad4 NFE exome

AF:

0.00378

Gnomad4 OTH exome

AF:

0.00853

GnomAD4 genome

AF:

0.0175

AC:

837

AN:

47910

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

AN XY:

13308

show subpopulations

Gnomad4 AFR

AF:

0.0563

Gnomad4 AMR

AF:

0.00976

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00821

Gnomad4 SAS

AF:

0.00674

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.0226

Alfa

AF:

0.00496

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

May 18, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.87

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

DANN

Benign

0.11

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0065

Sift4G

Benign

0.47

Vest4

0.16

MVP

0.068

ClinPred

0.0041

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