15-101274611-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018445.6(SELENOS):c.389G>T(p.Gly130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,613,562 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 155 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 144 hom. )

Consequence

SELENOS
NM_018445.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.32

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 Benign. Variant got -16 ACMG points.

BP6

Variant 15-101274611-C-A is Benign according to our data. Variant chr15-101274611-C-A is described in ClinVar as [Benign]. Clinvar id is 776948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_018445.6 link	c.389G>T	p.Gly130Val	missense_variant	Exon 4 of 6	ENST00000526049.6	NP_060915.2
SELENOS	NM_203472.3 link	c.389G>T	p.Gly130Val	missense_variant	Exon 4 of 7		NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000526049.6 link	c.389G>T	p.Gly130Val	missense_variant	Exon 4 of 6	1	NM_018445.6	ENSP00000433541.1		Q9BQE4

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4066

AN:

152184

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.00751

AC:

1865

AN:

248400

Hom.:

AF XY:

0.00641

AC XY:

864

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.0874

Gnomad AMR exome

AF:

0.00687

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000820

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.00763

GnomAD4 exome

AF:

0.00388

AC:

5665

AN:

1461260

Hom.:

144

Cov.:

AF XY:

0.00366

AC XY:

2659

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.0899

Gnomad4 AMR exome

AF:

0.00809

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000963

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00868

GnomAD4 genome

AF:

0.0267

AC:

4070

AN:

152302

Hom.:

155

Cov.:

AF XY:

0.0264

AC XY:

1963

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0880

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.00644

Hom.:

Bravo

AF:

0.0296

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0722

AC:

272

ESP6500EA

AF:

0.00122

AC:

ExAC

AF:

0.00842

AC:

1017

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;.;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

.;.;T;T

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;L;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Benign

0.054

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.20

T;T;T;.

Polyphen

0.15

B;.;B;.

Vest4

0.28

MVP

0.34

MPC

0.073

ClinPred

0.025

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.42

Position offset: 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