Genetic Variant NM_016378.3:c.274G>C (chrX-8170178-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_016378.3(VCX2):c.274G>C(p.Glu92Gln) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E92K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 7)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12

Publications

0 publications found

Variant links:

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]

VCX2 links:

ENSG00000285679 (HGNC:):

ENSG00000285679 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.126075).

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.274G>C	p.Glu92Gln	missense	Exon 3 of 3	NP_057462.2	Q9H322

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCX2	ENST00000317103.5	TSL:1 MANE Select	c.274G>C	p.Glu92Gln	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
ENSG00000285679	ENST00000649338.1		n.263-58157C>G		intron	N/A
ENSG00000285679	ENST00000659022.1		n.972-58157C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000631

AC:

AN:

158357

AF XY:

0.00

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000184

AC:

AN:

1087548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26182

American (AMR)

AF:

0.00

AC:

AN:

34649

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19221

East Asian (EAS)

AF:

0.00

AC:

AN:

29960

South Asian (SAS)

AF:

0.0000187

AC:

AN:

53602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39163

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2874

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

836267

Other (OTH)

AF:

0.00

AC:

AN:

45630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0048

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.62

M_CAP

Benign

0.0025

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

-1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

REVEL

Benign

0.13

Sift

Uncertain

0.013

Sift4G

Uncertain

0.019

Polyphen

0.77

Vest4

0.23

MutPred

0.062

Loss of glycosylation at P91 (P = 0.0652)

MVP

0.13

MPC

0.0091

ClinPred

0.11

GERP RS

0.046

Varity_R

0.24

gMVP

0.0018

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over