rs1389572258

Variant names:

• chrX-8170056-G-A
• rs1389572258
• NM_016378.3:c.396C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016378.3(VCX2):​c.396C>T​(p.Ser132Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,096,583 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.000016 (0 hom. 5 hem.)
• Consequence: VCX2 NM_016378.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

Genes affected

VCX2 (HGNC:18158): (variable charge X-linked 2) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes that are expressed exclusively in male germ cells. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. This gene contains two copies of a 30 nt tandem repeat. Deletion of a nearby member of this family was implicated in cognitive disability. [provided by RefSeq, Feb 2015]

ENSG00000285679 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-8170056-G-A is Benign according to our data. Variant chrX-8170056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3	c.396C>T	p.Ser132Ser	synonymous_variant	Exon 3 of 3	ENST00000317103.5	NP_057462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX2	ENST00000317103.5	c.396C>T	p.Ser132Ser	synonymous_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4
ENSG00000285679	ENST00000649338.1	n.263-58279G>A		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1	n.972-58279G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD3 exomes AF: 0.0000110 AC: 2 AN: 181746 Hom.: 0 AF XY: 0.0000296 AC XY: 2 AN XY: 67642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000144

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 17 AN: 1096583 Hom.: 0 Cov.: 76 AF XY: 0.0000138 AC XY: 5 AN XY: 362877

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.0000993

Gnomad4 SAS exome AF: 0.0000554

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 15

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VCX2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs1389572258; hg19: chrX-8138097;