NM_016379.4:c.534C>T

Variant names:

• chrX-6533772-G-A
• rs749452069
• NM_016379.4:c.534C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_016379.4(VCX3A):​c.534C>T​(p.Ser178Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,138,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. 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 0.00022 (0 hom., 1 hem., cov: 18)
  • Exomes 𝑓: 0.00019 (0 hom. 19 hem.)
• Consequence: VCX3A NM_016379.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.756 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 19 gene

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.534C>T	p.Ser178Ser	synonymous	Exon 3 of 3	NP_057463.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX3A	ENST00000381089.7	TSL:1 MANE Select	c.534C>T	p.Ser178Ser	synonymous	Exon 3 of 3	ENSP00000370479.3	Q9NNX9
	VCX3A	ENST00000898738.1		c.534C>T	p.Ser178Ser	synonymous	Exon 2 of 2	ENSP00000568797.1
	VCX3A	ENST00000398729.1	TSL:5	c.474C>T	p.Ser158Ser	synonymous	Exon 4 of 4	ENSP00000381713.1	E7ESE9

Frequencies

GnomAD3 genomes AF: 0.000221 AC: 22 AN: 99764 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000429

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000297

Gnomad SAS AF: 0.000505

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000332

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000133 AC: 24 AN: 179785 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000872

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.000192 AC: 199 AN: 1038811 Hom.: 0 Cov.: 38 AF XY: 0.0000552 AC XY: 19 AN XY: 344359

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25741

American (AMR) AF: 0.000391 AC: 13 AN: 33221

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17947

East Asian (EAS) AF: 0.0000695 AC: 2 AN: 28757

South Asian (SAS) AF: 0.000759 AC: 37 AN: 48773

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3253

European-Non Finnish (NFE) AF: 0.000179 AC: 143 AN: 800483

Other (OTH) AF: 0.0000924 AC: 4 AN: 43268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000220 AC: 22 AN: 99793 Hom.: 0 Cov.: 18 AF XY: 0.0000376 AC XY: 1 AN XY: 26583

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27301

American (AMR) AF: 0.000429 AC: 4 AN: 9333

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2403

East Asian (EAS) AF: 0.000298 AC: 1 AN: 3356

South Asian (SAS) AF: 0.000507 AC: 1 AN: 1972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5165

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.000332 AC: 16 AN: 48168

Other (OTH) AF: 0.00 AC: 0 AN: 1310

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000024758), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs749452069; hg19: chrX-6451813;