Genetic Variant NM_016379.4:c.*2C>T (chrX-6533743-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_016379.4(VCX3A):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 1,170,883 control chromosomes in the GnomAD database, including 88 homozygotes. There are 1,767 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 0.0083 ( 11 hom., 102 hem., cov: 18)

Exomes 𝑓: 0.0079 ( 77 hom. 1665 hem. )

Consequence

VCX3A
NM_016379.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.328

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049083203).

BP6

Variant X-6533743-G-A is Benign according to our data. Variant chrX-6533743-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3057107.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4 link	c.*2C>T		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.*2C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 link	c.*2C>T		downstream_gene_variant		5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.00826

AC:

835

AN:

101098

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

102

AN XY:

26212

show subpopulations

Gnomad AFR

AF:

0.00134

Gnomad AMI

AF:

0.0405

Gnomad AMR

AF:

0.00633

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000290

Gnomad SAS

AF:

0.00235

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00842

GnomAD3 exomes

AF:

0.00367

AC:

653

AN:

177733

Hom.:

AF XY:

0.00206

AC XY:

136

AN XY:

65875

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00573

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00210

Gnomad FIN exome

AF:

0.00534

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00788

AC:

8426

AN:

1069744

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

1665

AN XY:

353512

show subpopulations

Gnomad4 AFR exome

AF:

0.000649

Gnomad4 AMR exome

AF:

0.00433

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00408

Gnomad4 FIN exome

AF:

0.00657

Gnomad4 NFE exome

AF:

0.00883

Gnomad4 OTH exome

AF:

0.00658

GnomAD4 genome

AF:

0.00826

AC:

835

AN:

101139

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

102

AN XY:

26255

show subpopulations

Gnomad4 AFR

AF:

0.00134

Gnomad4 AMR

AF:

0.00632

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.000291

Gnomad4 SAS

AF:

0.00237

Gnomad4 FIN

AF:

0.00828

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00831

Alfa

AF:

0.00629

Hom.:

ESP6500AA

AF:

0.00367

AC:

ESP6500EA

AF:

0.0164

AC:

110

ExAC

AF:

0.0139

AC:

1680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VCX3A-related disorder

Benign:1

May 30, 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

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.5

DANN

Benign

0.49

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.29

MetaRNN

Benign

0.049

Sift4G

Benign

0.14

Vest4

0.12

ClinPred

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