Genetic Variant NM_016379.4:c.556G>T (chrX-6533750-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016379.4(VCX3A):c.556G>T(p.Val186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 891,927 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V186M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0000022 ( 0 hom. 0 hem. )

Consequence

VCX3A
NM_016379.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.735

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058758497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX3A	NM_016379.4	MANE Select	c.556G>T	p.Val186Leu	missense	Exon 3 of 3	NP_057463.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCX3A	ENST00000381089.7	TSL:1 MANE Select	c.556G>T	p.Val186Leu	missense	Exon 3 of 3	ENSP00000370479.3	Q9NNX9
VCX3A	ENST00000898738.1		c.556G>T	p.Val186Leu	missense	Exon 2 of 2	ENSP00000568797.1
VCX3A	ENST00000398729.1	TSL:5	c.496G>T	p.Val166Leu	missense	Exon 4 of 4	ENSP00000381713.1	E7ESE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000224

AC:

AN:

891927

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

305889

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20272

American (AMR)

AF:

0.00

AC:

AN:

30757

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14234

East Asian (EAS)

AF:

0.00

AC:

AN:

29491

South Asian (SAS)

AF:

0.00

AC:

AN:

46407

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34371

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2992

European-Non Finnish (NFE)

AF:

0.00000296

AC:

AN:

675949

Other (OTH)

AF:

0.00

AC:

AN:

37454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.6

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0018

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.40

M_CAP

Benign

0.0012

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.73

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.20

REVEL

Benign

0.016

Sift

Pathogenic

0.0

Sift4G

Benign

0.29

Polyphen

0.86

Vest4

0.054

MutPred

0.23

Gain of helix (P = 0.132)

MVP

0.043

MPC

0.26

ClinPred

0.13

GERP RS

0.46

Varity_R

0.20

gMVP

0.0077

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over