rs139229818

Variant names:

• chrX-8170163-C-T
• rs139229818
• NM_016378.3:c.289G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-8170163-C-T
• chrX-8170163-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016378.3(VCX2):​c.289G>A​(p.Glu97Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 1,136,458 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.0000074 (0 hom. 7 hem.)
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.775
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1503433).
• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

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.289G>A	p.Glu97Lys	missense	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.289G>A	p.Glu97Lys	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58172C>T		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58172C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000182 AC: 1 AN: 54858 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00165

GnomAD2 exomes AF: 0.0000130 AC: 2 AN: 154095 AF XY: 0.0000431

Gnomad AFR exome AF: 0.0000902

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000740 AC: 8 AN: 1081613 Hom.: 0 Cov.: 31 AF XY: 0.0000199 AC XY: 7 AN XY: 351329

African (AFR) AF: 0.0000390 AC: 1 AN: 25658

American (AMR) AF: 0.0000293 AC: 1 AN: 34092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19143

East Asian (EAS) AF: 0.00 AC: 0 AN: 29864

South Asian (SAS) AF: 0.0000755 AC: 4 AN: 52946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2878

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832648

Other (OTH) AF: 0.0000440 AC: 2 AN: 45426

GnomAD4 genome AF: 0.0000182 AC: 1 AN: 54845 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6263

⚠️ 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: 13241

American (AMR) AF: 0.00 AC: 0 AN: 3900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1653

East Asian (EAS) AF: 0.00 AC: 0 AN: 1245

South Asian (SAS) AF: 0.00 AC: 0 AN: 778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2459

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 73

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 30499

Other (OTH) AF: 0.00162 AC: 1 AN: 616

⚠️ 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: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.78
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.047
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.29
MutPred		0.20		Gain of ubiquitination at E97 (P = 0.0014)
MVP		0.18
MPC		0.0090
ClinPred		0.49	T
GERP RS		0.046
Varity_R		0.58
gMVP		0.0047
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: rs139229818; hg19: chrX-8138204;