Genetic Variant VCX:p.Leu164Pro (chrX-7843886-T-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_001393662.1(VCX):c.491T>C(p.Leu164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., 0 hem., cov: 10)

Exomes 𝑓: 0.0000087 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

VCX
NM_001393662.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: -0.717

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09428781).

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.491T>C	p.Leu164Pro	missense	Exon 2 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.491T>C	p.Leu164Pro	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.491T>C	p.Leu164Pro	missense	Exon 2 of 2	ENSP00000509688.1	Q9H320
VCX	ENST00000381059.7	TSL:1	c.491T>C	p.Leu164Pro	missense	Exon 3 of 3	ENSP00000370447.3	Q9H320
VCX	ENST00000341408.6	TSL:5	c.431T>C	p.Leu144Pro	missense	Exon 3 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes

AF:

0.0000610

AC:

AN:

65544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000618

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000921

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000573

AC:

AN:

174627

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:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000865

AC:

AN:

1040001

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

329307

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25344

American (AMR)

AF:

0.00

AC:

AN:

34369

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18068

East Asian (EAS)

AF:

0.0000676

AC:

AN:

29602

South Asian (SAS)

AF:

0.00

AC:

AN:

49986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38239

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2777

European-Non Finnish (NFE)

AF:

0.00000877

AC:

AN:

797868

Other (OTH)

AF:

0.00

AC:

AN:

43748

⚠️ 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: 0.308

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000610

AC:

AN:

65546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11292

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

18779

American (AMR)

AF:

0.00

AC:

AN:

5194

Ashkenazi Jewish (ASJ)

AF:

0.000618

AC:

AN:

1618

East Asian (EAS)

AF:

0.00

AC:

AN:

2250

South Asian (SAS)

AF:

0.00

AC:

AN:

1121

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.0000921

AC:

AN:

32560

Other (OTH)

AF:

0.00

AC:

AN:

810

⚠️ 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: 0.263

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000274

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.59

M_CAP

Benign

0.0032

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-0.72

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.0080

Sift

Benign

0.041

Sift4G

Benign

0.10

Polyphen

0.0020

Vest4

0.084

MVP

0.043

MPC

0.57

ClinPred

0.039

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.0037

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over