X-8465889-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001888.4(VCX3B):​c.247G>A​(p.Glu83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 13)

Consequence

VCX3B
NM_001001888.4 missense

Scores

1
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13692832).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VCX3BNM_001001888.4 linkuse as main transcriptc.247G>A p.Glu83Lys missense_variant 3/3 ENST00000381032.6 NP_001001888.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VCX3BENST00000381032.6 linkuse as main transcriptc.247G>A p.Glu83Lys missense_variant 3/35 NM_001001888.4 ENSP00000370420 P1Q9H321-1

Frequencies

GnomAD3 genomes
Cov.:
13
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
13

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 07, 2024The c.247G>A (p.E83K) alteration is located in exon 3 (coding exon 2) of the VCX3B gene. This alteration results from a G to A substitution at nucleotide position 247, causing the glutamic acid (E) at amino acid position 83 to be replaced by a lysine (K). 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
0.19
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0054
.;T;.;.
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
.;L;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.044
Sift
Pathogenic
0.0
D;D;T;D
Sift4G
Benign
0.11
T;T;D;T
Polyphen
0.98
.;D;.;.
Vest4
0.20
MutPred
0.27
Gain of ubiquitination at E83 (P = 0.0018);Gain of ubiquitination at E83 (P = 0.0018);Gain of ubiquitination at E83 (P = 0.0018);Gain of ubiquitination at E83 (P = 0.0018);
MVP
0.092
MPC
1.0
ClinPred
0.29
T
GERP RS
0.49
Varity_R
0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-8433930; API