Genetic Variant VCX2:p.Pro103Ala (chrX-8170145-G-C) – 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.307C>G(p.Pro103Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P103T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., 0 hem., cov: 8)

Exomes 𝑓: 0.0000029 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.236

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=0.14621097).

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.307C>G	p.Pro103Ala	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.307C>G	p.Pro103Ala	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
ENSG00000285679	ENST00000649338.1		n.263-58190G>C		intron	N/A
ENSG00000285679	ENST00000659022.1		n.972-58190G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000174

AC:

AN:

57321

Hom.:

Cov.:

show subpopulations

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:

0.0000315

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000289

AC:

AN:

1037712

Hom.:

Cov.:

AF XY:

0.00000631

AC XY:

AN XY:

316856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25319

American (AMR)

AF:

0.00

AC:

AN:

32216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18471

East Asian (EAS)

AF:

0.00

AC:

AN:

29304

South Asian (SAS)

AF:

0.00

AC:

AN:

50032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2793

European-Non Finnish (NFE)

AF:

0.00000376

AC:

AN:

797368

Other (OTH)

AF:

0.00

AC:

AN:

43969

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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

AF:

0.0000174

AC:

AN:

57321

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6577

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13709

American (AMR)

AF:

0.00

AC:

AN:

4221

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1690

East Asian (EAS)

AF:

0.00

AC:

AN:

1397

South Asian (SAS)

AF:

0.00

AC:

AN:

856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

31751

Other (OTH)

AF:

0.00

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.74

M_CAP

Benign

0.0022

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PhyloP100

0.24

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.031

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.88

Vest4

0.13

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.10

MPC

0.0092

ClinPred

0.58

GERP RS

0.046

Varity_R

0.28

gMVP

0.0019

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