Genetic Variant VCX:p.Pro3Ser (chrX-7843210-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001393662.1(VCX):c.7C>T(p.Pro3Ser) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.0043 ( 0 hom. 48 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0900

Publications

1 publications found

Variant links:

Genes affected

VCX (HGNC:12667): (variable charge X-linked) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes, and all are expressed exclusively in male germ cells. The X-linked members are clustered on chromosome Xp22 and Y-linked members are two identical copies of the gene within a palindromic region on Yq11. The family members share a high degree of sequence identity, with the exception that a 30-bp unit is tandemly repeated in X-linked members but occurs only once in Y-linked members. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. This gene contains 10 repeats of the 30-bp unit. [provided by RefSeq, Jul 2008]

VCX links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008450568).

BP6

Variant X-7843210-C-T is Benign according to our data. Variant chrX-7843210-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3025302.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393662.1. 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
	VCX	NM_001393662.1	MANE Select	c.7C>T	p.Pro3Ser	missense	Exon 1 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.7C>T	p.Pro3Ser	missense	Exon 2 of 3	NP_038480.2	Q9H320

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCX	ENST00000688183.1	MANE Select	c.7C>T	p.Pro3Ser	missense	Exon 1 of 2	ENSP00000509688.1	Q9H320
VCX	ENST00000381059.7	TSL:1	c.7C>T	p.Pro3Ser	missense	Exon 2 of 3	ENSP00000370447.3	Q9H320
VCX	ENST00000341408.6	TSL:5	c.7C>T	p.Pro3Ser	missense	Exon 1 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

251

AN:

98506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000433

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00574

Gnomad ASJ

AF:

0.00129

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000651

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00374

Gnomad OTH

AF:

0.00157

GnomAD2 exomes

AF:

0.000833

AC:

126

AN:

151242

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.000280

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00435

AC:

4659

AN:

1071488

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

348952

show subpopulations

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

African (AFR)

AF:

0.000572

AC:

AN:

26235

American (AMR)

AF:

0.00204

AC:

AN:

34766

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

18874

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30122

South Asian (SAS)

AF:

0.000410

AC:

AN:

53687

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

39693

Middle Eastern (MID)

AF:

0.00284

AC:

AN:

2816

European-Non Finnish (NFE)

AF:

0.00524

AC:

4301

AN:

820310

Other (OTH)

AF:

0.00371

AC:

167

AN:

44985

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.288

Heterozygous variant carriers

464

927

1391

1854

2318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.00255

AC:

251

AN:

98543

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24157

show subpopulations

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

African (AFR)

AF:

0.000432

AC:

AN:

27782

American (AMR)

AF:

0.00573

AC:

AN:

9248

Ashkenazi Jewish (ASJ)

AF:

0.00129

AC:

AN:

2330

East Asian (EAS)

AF:

0.00

AC:

AN:

2944

South Asian (SAS)

AF:

0.00

AC:

AN:

1981

European-Finnish (FIN)

AF:

0.000651

AC:

AN:

4607

Middle Eastern (MID)

AF:

0.00

AC:

AN:

177

European-Non Finnish (NFE)

AF:

0.00374

AC:

178

AN:

47581

Other (OTH)

AF:

0.00155

AC:

AN:

1290

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00254

Hom.:

ESP6500AA

AF:

0.000529

AC:

ESP6500EA

AF:

0.00608

AC:

ExAC

AF:

0.00383

AC:

423

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.65

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.090

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.55

REVEL

Benign

0.021

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.014

Polyphen

0.99

Vest4

0.11

MVP

0.043

MPC

0.36

ClinPred

0.020

GERP RS

0.17

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.14

gMVP

0.0079

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over