Genetic Variant NM_016379.4:c.504C>T (chrX-6533802-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_016379.4(VCX3A):c.504C>T(p.Ser168Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.000059 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

VCX3A
NM_016379.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.272

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=0.272 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX3A	NM_016379.4 link	c.504C>T	p.Ser168Ser	synonymous_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	ENST00000381089.7 link	c.504C>T	p.Ser168Ser	synonymous_variant	Exon 3 of 3	1	NM_016379.4	ENSP00000370479.3		Q9NNX9
VCX3A	ENST00000398729.1 link	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 4 of 4	5		ENSP00000381713.1		E7ESE9

Frequencies

GnomAD3 genomes

AF:

0.000373

AC:

AN:

96583

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24759

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000432

Gnomad EAS

AF:

0.000324

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000127

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000595

AC:

AN:

1025243

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

338291

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000110

Gnomad4 SAS exome

AF:

0.0000417

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.000373

AC:

AN:

96610

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24800

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000432

Gnomad4 EAS

AF:

0.000326

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000127

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.3

DANN

Benign

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over