X-8170119-T-C

Variant names:

• chrX-8170119-T-C
• rs1058238
• NM_016378.3:c.333A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_016378.3(VCX2):​c.333A>G​(p.Glu111Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (20893 hom., 5478 hem., cov: 10)
  • Exomes 𝑓: 0.83 (189589 hom. 252579 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.816
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.18).
• BP6: Variant X-8170119-T-C is Benign according to our data. Variant chrX-8170119-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 769171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.816 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016378.3. 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
	VCX2	NM_016378.3	MANE Select	c.333A>G	p.Glu111Glu	synonymous	Exon 3 of 3	NP_057462.2	Q9H322

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX2	ENST00000317103.5	TSL:1 MANE Select	c.333A>G	p.Glu111Glu	synonymous	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58216T>C		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58216T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.787 AC: 56071 AN: 71215 Hom.: 20896 Cov.: 10

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.797

GnomAD2 exomes AF: 0.843 AC: 119103 AN: 141297 AF XY: 0.812

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.925

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.963

Gnomad FIN exome AF: 0.767

Gnomad NFE exome AF: 0.804

Gnomad OTH exome AF: 0.829

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.829 AC: 674229 AN: 812829 Hom.: 189589 Cov.: 41 AF XY: 0.792 AC XY: 252579 AN XY: 318863

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

African (AFR) AF: 0.920 AC: 19660 AN: 21362

American (AMR) AF: 0.914 AC: 26615 AN: 29107

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 12498 AN: 15960

East Asian (EAS) AF: 0.967 AC: 27586 AN: 28516

South Asian (SAS) AF: 0.827 AC: 38752 AN: 46856

European-Finnish (FIN) AF: 0.770 AC: 28330 AN: 36815

Middle Eastern (MID) AF: 0.798 AC: 2104 AN: 2636

European-Non Finnish (NFE) AF: 0.820 AC: 488255 AN: 595133

Other (OTH) AF: 0.835 AC: 30429 AN: 36444

⚠️ 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 Data not reliable, filtered out with message: InbreedingCoeff AF: 0.787 AC: 56072 AN: 71220 Hom.: 20893 Cov.: 10 AF XY: 0.568 AC XY: 5478 AN XY: 9638

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

African (AFR) AF: 0.873 AC: 15546 AN: 17808

American (AMR) AF: 0.842 AC: 4888 AN: 5806

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 1397 AN: 1943

East Asian (EAS) AF: 0.935 AC: 1905 AN: 2038

South Asian (SAS) AF: 0.681 AC: 788 AN: 1157

European-Finnish (FIN) AF: 0.630 AC: 1928 AN: 3060

Middle Eastern (MID) AF: 0.826 AC: 90 AN: 109

European-Non Finnish (NFE) AF: 0.750 AC: 28439 AN: 37934

Other (OTH) AF: 0.793 AC: 719 AN: 907

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.819 Hom.: 4612

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.93
DANN	Benign	0.20
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs1058238; hg19: chrX-8138160; COSMIC: COSV57703563;