rs145708656

Variant names:

• chrX-8170037-C-G
• rs145708656
• NM_016378.3:c.415G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-8170037-C-G
• chrX-8170037-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016378.3(VCX2):​c.415G>C​(p.Asp139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D139N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 1 hem., cov: 13)
  • Exomes 𝑓: 0.000061 (1 hom. 24 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07181105).

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.415G>C	p.Asp139His	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.415G>C	p.Asp139His	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58298C>G		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58298C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000544 AC: 5 AN: 91839 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000410

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: 0.0000860

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000331 AC: 6 AN: 181495 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000746

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000611 AC: 67 AN: 1096478 Hom.: 1 Cov.: 31 AF XY: 0.0000661 AC XY: 24 AN XY: 362828

African (AFR) AF: 0.00 AC: 0 AN: 26380

American (AMR) AF: 0.0000284 AC: 1 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 54102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39627

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 0.0000784 AC: 66 AN: 841825

Other (OTH) AF: 0.00 AC: 0 AN: 46000

GnomAD4 genome AF: 0.0000544 AC: 5 AN: 91839 Hom.: 0 Cov.: 13 AF XY: 0.0000578 AC XY: 1 AN XY: 17305

African (AFR) AF: 0.0000410 AC: 1 AN: 24415

American (AMR) AF: 0.00 AC: 0 AN: 8041

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2336

East Asian (EAS) AF: 0.00 AC: 0 AN: 2765

South Asian (SAS) AF: 0.00 AC: 0 AN: 1664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 199

European-Non Finnish (NFE) AF: 0.0000860 AC: 4 AN: 46520

Other (OTH) AF: 0.00 AC: 0 AN: 1197

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.000125

ExAC AF: 0.0000415 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.74
DEOGEN2	Benign	0.0039	T
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.059
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.19
MutPred		0.17		Gain of glycosylation at T138 (P = 0.0711)
MVP		0.014
MPC		0.0089
ClinPred		0.068	T
GERP RS		0.19
Varity_R		0.099
gMVP		0.0040
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: rs145708656; hg19: chrX-8138078;