rs780152424

Variant names:

• chrX-8170164-G-C
• rs780152424
• NM_016378.3:c.288C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-8170164-G-C
• chrX-8170164-G-A

Variant summary

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

The NM_016378.3(VCX2):​c.288C>G​(p.Ser96Arg) variant causes a missense 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S96I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07
• 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=0.13695753).

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.288C>G	p.Ser96Arg	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.288C>G	p.Ser96Arg	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58171G>C		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58171G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 53767 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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000279 AC: 3 AN: 1076010 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 1 AN XY: 349672

African (AFR) AF: 0.00 AC: 0 AN: 25833

American (AMR) AF: 0.00 AC: 0 AN: 33993

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19060

East Asian (EAS) AF: 0.00 AC: 0 AN: 29712

South Asian (SAS) AF: 0.00 AC: 0 AN: 52730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000362 AC: 3 AN: 828611

Other (OTH) AF: 0.00 AC: 0 AN: 45108

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 53767 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6153

African (AFR) AF: 0.00 AC: 0 AN: 12969

American (AMR) AF: 0.00 AC: 0 AN: 3829

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1626

East Asian (EAS) AF: 0.00 AC: 0 AN: 1222

South Asian (SAS) AF: 0.00 AC: 0 AN: 763

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2367

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 79

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29952

Other (OTH) AF: 0.00 AC: 0 AN: 600

Alfa AF: 0.00 Hom.: 1

ExAC AF: 0.0000177 AC: 2

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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.80
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.034
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.017	D
Polyphen		0.90	P
Vest4		0.14
MutPred		0.11		Loss of phosphorylation at S96 (P = 0.0134)
MVP		0.19
MPC		0.0090
ClinPred		0.39	T
GERP RS		0.046
Varity_R		0.53
gMVP		0.0011
Mutation Taster		=99/1	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: rs780152424; hg19: chrX-8138205;