X-8465457-C-T

Position:

chrX-8465457-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001001888.4(VCX3B):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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., 0 hem., cov: 16)

Exomes 𝑓: 0.00070 ( 2 hom. 72 hem. )

Failed GnomAD Quality Control

Consequence

VCX3B
NM_001001888.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: -0.838

Variant links:

Genes affected

VCX3B (HGNC:31838): (variable charge X-linked 3B) 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 the Y-linked members are two identical copies of the gene within a palindromic region on chromosome Yq11. The family members share a high degree of sequence identity, with the exception that a 30-nt 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. This family member, as represented by the reference genome allele, contains 14 copies of the 30-nt repeat unit. VCX/Y genes encode small and highly charged proteins containing putative bipartite nuclear localization signals. Although the exact function of this family member has yet to be determined, a role in mRNA stability regulation can be inferred from the ability of the highly similar family member, VCX-A, to inhibit mRNA decapping. A possible role in the regulation of ribosome assembly during spermatogenesis has also been suggested. [provided by RefSeq, Aug 2010]

VCX3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0874379).

BP6

Variant X-8465457-C-T is Benign according to our data. Variant chrX-8465457-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1206080.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX3B	NM_001001888.4 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	2/3	ENST00000381032.6	NP_001001888.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCX3B	ENST00000381032.6 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	2/3	5	NM_001001888.4	ENSP00000370420	P1	Q9H321-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

310

AN:

86874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19046

FAILED QC

Gnomad AFR

AF:

0.000504

Gnomad AMI

AF:

0.00385

Gnomad AMR

AF:

0.00776

Gnomad ASJ

AF:

0.00180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000739

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00426

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000702

AC:

672

AN:

956810

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

278894

show subpopulations

Gnomad4 AFR exome

AF:

0.000166

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000207

Gnomad4 FIN exome

AF:

0.000347

Gnomad4 NFE exome

AF:

0.000737

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00357

AC:

310

AN:

86899

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19089

show subpopulations

Gnomad4 AFR

AF:

0.000503

Gnomad4 AMR

AF:

0.00775

Gnomad4 ASJ

AF:

0.00180

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000739

Gnomad4 NFE

AF:

0.00520

Gnomad4 OTH

AF:

0.00421

Alfa

AF:

0.00510

Hom.:

ExAC

AF:

0.0000436

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	VCX3B: BP4 -
Uncertain significance, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.7C>T (p.P3S) alteration is located in exon 2 (coding exon 1) of the VCX3B gene. This alteration results from a C to T substitution at nucleotide position 7, causing the proline (P) at amino acid position 3 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0084

.;T;.;.

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.087

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.85

N;N;N;N

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.34

T;T;D;T

Polyphen

0.97

.;D;.;.

Vest4

0.063

MVP

0.014

MPC

0.93

ClinPred

0.034

GERP RS

-0.84

Varity_R

0.19

gMVP

0.0091

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over