dbSNP rs1283430603: SELENOS:p.Glu91Lys (chr15-101275302-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018445.6(SELENOS):c.271G>A(p.Glu91Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SELENOS
NM_018445.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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]

SELENOS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_018445.6 link	c.271G>A	p.Glu91Lys	missense_variant	Exon 3 of 6	ENST00000526049.6	NP_060915.2
SELENOS	NM_203472.3 link	c.271G>A	p.Glu91Lys	missense_variant	Exon 3 of 7		NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000526049.6 link	c.271G>A	p.Glu91Lys	missense_variant	Exon 3 of 6	1	NM_018445.6	ENSP00000433541.1		Q9BQE4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000492

AC:

AN:

203114

Hom.:

AF XY:

0.00000918

AC XY:

AN XY:

108966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000652

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428970

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271G>A (p.E91K) alteration is located in exon 3 (coding exon 3) of the VIMP gene. This alteration results from a G to A substitution at nucleotide position 271, causing the glutamic acid (E) at amino acid position 91 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

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.;T;.

Eigen

Benign

0.036

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

.;.;D;D

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.8

M;.;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.043

D;D;D;.

Polyphen

0.0030

B;.;B;.

Vest4

0.46

MutPred

0.74

Gain of MoRF binding (P = 0.0082);.;Gain of MoRF binding (P = 0.0082);.;

MVP

0.18

MPC

0.21

ClinPred

0.87

GERP RS

5.0

Varity_R

0.79

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