X-8170156-G-C

Variant names:

• chrX-8170156-G-C
• rs142216536
• NM_016378.3:c.296C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_016378.3(VCX2):​c.296C>G​(p.Thr99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.000019 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49
• 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=0.03831759).
• BP6: Variant X-8170156-G-C is Benign according to our data. Variant chrX-8170156-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2221361.Status of the report is criteria_provided_single_submitter, 1 stars.

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.296C>G	p.Thr99Ser	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.296C>G	p.Thr99Ser	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58179G>C		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58179G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 55435 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

GnomAD2 exomes AF: 0.0000215 AC: 2 AN: 93184 AF XY: 0.00

Gnomad AFR exome AF: 0.000146

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: 0.0000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000188 AC: 20 AN: 1065386 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 343420

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

African (AFR) AF: 0.00 AC: 0 AN: 25567

American (AMR) AF: 0.00 AC: 0 AN: 33349

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18918

East Asian (EAS) AF: 0.0000338 AC: 1 AN: 29589

South Asian (SAS) AF: 0.00 AC: 0 AN: 52082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37451

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2838

European-Non Finnish (NFE) AF: 0.0000231 AC: 19 AN: 820891

Other (OTH) AF: 0.00 AC: 0 AN: 44701

⚠️ 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: AC0 AF: 0.00 AC: 0 AN: 55435 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6367

African (AFR) AF: 0.00 AC: 0 AN: 13307

American (AMR) AF: 0.00 AC: 0 AN: 4027

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1659

East Asian (EAS) AF: 0.00 AC: 0 AN: 1326

South Asian (SAS) AF: 0.00 AC: 0 AN: 825

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2467

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 83

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 30757

Other (OTH) AF: 0.00 AC: 0 AN: 610

Alfa AF: 0.0000510 Hom.: 1

ESP6500AA AF: 0.00478 AC: 18

ESP6500EA AF: 0.00242 AC: 16

ExAC AF: 0.0000288 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.083
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.18
DEOGEN2	Benign	0.0087	T
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.58	N
PhyloP100		-1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.026
Sift	Benign	0.18	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.11		Loss of glycosylation at T99 (P = 0.0648)
MVP		0.061
MPC		0.0093
ClinPred		0.025	T
GERP RS		-0.093
Varity_R		0.13
gMVP		0.0016
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: rs142216536; hg19: chrX-8138197;