Genetic Variant NM_001393662.1:c.568G>A (chrX-7843963-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393662.1(VCX):c.568G>A(p.Val190Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., 2 hem., cov: 11)

Exomes 𝑓: 0.0058 ( 63 hom. 761 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065913796).

BP6

Variant X-7843963-G-A is Benign according to our data. Variant chrX-7843963-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2659919.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

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.568G>A	p.Val190Met	missense	Exon 2 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.568G>A	p.Val190Met	missense	Exon 3 of 3	NP_038480.2	Q9H320

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCX	ENST00000688183.1	MANE Select	c.568G>A	p.Val190Met	missense	Exon 2 of 2	ENSP00000509688.1	Q9H320
VCX	ENST00000381059.7	TSL:1	c.568G>A	p.Val190Met	missense	Exon 3 of 3	ENSP00000370447.3	Q9H320
VCX	ENST00000341408.6	TSL:5	c.508G>A	p.Val170Met	missense	Exon 3 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

301

AN:

71190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000592

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00156

Gnomad ASJ

AF:

0.00772

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00607

Gnomad FIN

AF:

0.00704

Gnomad MID

AF:

0.00800

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.00341

GnomAD2 exomes

AF:

0.000855

AC:

151

AN:

176617

AF XY:

0.000593

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.000223

Gnomad ASJ exome

AF:

0.000550

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00412

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00583

AC:

4131

AN:

708099

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

761

AN XY:

225989

show subpopulations

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

African (AFR)

AF:

0.000441

AC:

AN:

15864

American (AMR)

AF:

0.00269

AC:

AN:

21551

Ashkenazi Jewish (ASJ)

AF:

0.00474

AC:

AN:

12650

East Asian (EAS)

AF:

0.0000404

AC:

AN:

24745

South Asian (SAS)

AF:

0.00579

AC:

231

AN:

39864

European-Finnish (FIN)

AF:

0.0127

AC:

411

AN:

32487

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

2213

European-Non Finnish (NFE)

AF:

0.00598

AC:

3153

AN:

527410

Other (OTH)

AF:

0.00581

AC:

182

AN:

31315

⚠️ 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: 0.384

Heterozygous variant carriers

189

378

566

755

944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.00421

AC:

300

AN:

71203

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

13349

show subpopulations

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

African (AFR)

AF:

0.000591

AC:

AN:

20293

American (AMR)

AF:

0.00157

AC:

AN:

5749

Ashkenazi Jewish (ASJ)

AF:

0.00772

AC:

AN:

1685

East Asian (EAS)

AF:

0.00

AC:

AN:

2264

South Asian (SAS)

AF:

0.00612

AC:

AN:

1307

European-Finnish (FIN)

AF:

0.00704

AC:

AN:

2984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00660

AC:

234

AN:

35466

Other (OTH)

AF:

0.00334

AC:

AN:

898

⚠️ 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: 0.317

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00455

Hom.:

ExAC

AF:

0.00428

AC:

494

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

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.00026

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.26

PhyloP100

-1.3

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.73

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Benign

0.11

Polyphen

0.96

Vest4

0.067

MVP

0.043

MPC

0.35

ClinPred

0.0089

Varity_R

0.11

gMVP

0.0032

Mutation Taster

=100/0

polymorphism (auto)

(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