Genetic Variant SELENOS:p.Lys77Glu (chr15-101275344-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018445.6(SELENOS):c.229A>G(p.Lys77Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000621 in 1,577,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

SELENOS
NM_018445.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059395224).

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.229A>G	p.Lys77Glu	missense	Exon 3 of 6	NP_060915.2
	SELENOS	NM_203472.3		c.229A>G	p.Lys77Glu	missense	Exon 3 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.229A>G	p.Lys77Glu	missense	Exon 3 of 6	ENSP00000433541.1	Q9BQE4
SELENOS	ENST00000398226.8	TSL:1	c.229A>G	p.Lys77Glu	missense	Exon 3 of 7	ENSP00000381282.3	Q9BQE4
SELENOS	ENST00000528346.1	TSL:3	c.349A>G	p.Lys117Glu	missense	Exon 3 of 6	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000170

AC:

AN:

193852

AF XY:

0.000173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000599

Gnomad ASJ exome

AF:

0.00122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.000589

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1424974

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

705462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32830

American (AMR)

AF:

0.000525

AC:

AN:

38076

Ashkenazi Jewish (ASJ)

AF:

0.00169

AC:

AN:

25444

East Asian (EAS)

AF:

0.00

AC:

AN:

38904

South Asian (SAS)

AF:

0.00

AC:

AN:

80800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1092678

Other (OTH)

AF:

0.0000508

AC:

AN:

59012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000105

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41560

American (AMR)

AF:

0.000457

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000203

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000585

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

M_CAP

Benign

0.0046

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.1

PhyloP100

3.6

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Benign

0.23

Sift4G

Uncertain

0.043

Polyphen

0.72

Vest4

0.28

MutPred

0.57

Loss of methylation at K77 (P = 0.006)

MVP

0.20

MPC

0.20

ClinPred

0.15

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.56

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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