15-101274611-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018445.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOS	NM_018445.6	MANE Select	c.389G>T	p.Gly130Val	missense	Exon 4 of 6	NP_060915.2
	SELENOS	NM_203472.3		c.389G>T	p.Gly130Val	missense	Exon 4 of 7	NP_982298.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SELENOS	ENST00000526049.6	TSL:1 MANE Select	c.389G>T	p.Gly130Val	missense	Exon 4 of 6	ENSP00000433541.1	Q9BQE4
SELENOS	ENST00000398226.8	TSL:1	c.389G>T	p.Gly130Val	missense	Exon 4 of 7	ENSP00000381282.3	Q9BQE4
SELENOS	ENST00000528346.1	TSL:3	c.509G>T	p.Gly170Val	missense	Exon 4 of 6	ENSP00000434842.1	E9PN30

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

GnomAD2 exomes

AF:

0.00751

AC:

1865

AN:

248400

AF XY:

0.00641

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 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

African (AFR)

AF:

0.0899

AC:

3003

AN:

33418

American (AMR)

AF:

0.00809

AC:

361

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000963

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00141

AC:

1570

AN:

1111744

Other (OTH)

AF:

0.00868

AC:

524

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

278

556

833

1111

1389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0267

AC:

4070

AN:

152302

Hom.:

155

Cov.:

AF XY:

0.0264

AC XY:

1963

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0880

AC:

3655

AN:

41550

American (AMR)

AF:

0.0145

AC:

222

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00184

AC:

125

AN:

68026

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

203

405

608

810

1013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0107

Hom.:

123

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

3.3

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.054

Sift

Benign

0.27

Sift4G

Benign

0.20

Polyphen

0.15

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

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over