15-101274666-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018445.6(SELENOS):​c.334A>T​(p.Arg112Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SELENOS
NM_018445.6 missense

Scores

7
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
Variant links:
Genes affected
SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELENOSNM_018445.6 linkc.334A>T p.Arg112Trp missense_variant Exon 4 of 6 ENST00000526049.6 NP_060915.2
SELENOSNM_203472.3 linkc.334A>T p.Arg112Trp missense_variant Exon 4 of 7 NP_982298.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENOSENST00000526049.6 linkc.334A>T p.Arg112Trp missense_variant Exon 4 of 6 1 NM_018445.6 ENSP00000433541.1 Q9BQE4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1458956
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725684
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334A>T (p.R112W) alteration is located in exon 4 (coding exon 4) of the VIMP gene. This alteration results from a A to T substitution at nucleotide position 334, causing the arginine (R) at amino acid position 112 to be replaced by a tryptophan (W). 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
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.33
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T;.;T;.
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.97
.;.;D;D
M_CAP
Benign
0.030
D
MetaRNN
Pathogenic
0.78
D;D;D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Pathogenic
3.3
M;.;M;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-7.3
D;D;D;D
REVEL
Pathogenic
0.72
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;.
Polyphen
1.0
D;.;D;.
Vest4
0.81
MutPred
0.63
Loss of methylation at K115 (P = 0.0552);.;Loss of methylation at K115 (P = 0.0552);.;
MVP
0.33
MPC
0.24
ClinPred
0.98
D
GERP RS
1.8
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.87

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: chr15-101814871; API