Genetic Variant SELENOS:c.*565G>C (chr15-101271088-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000398226.8(SELENOS):c.*565G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,256 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 86 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

SELENOS
ENST00000398226.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.583

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_203472.3 link	c.*571G>C		3_prime_UTR_variant	Exon 7 of 7		NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000398226.8 link	c.*565G>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000381282.3		Q9BQE4

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3845

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00664

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0440

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0384

Gnomad OTH

AF:

0.0259

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0252

AC:

3840

AN:

152248

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1791

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00662

AC:

275

AN:

41534

American (AMR)

AF:

0.0178

AC:

273

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5190

South Asian (SAS)

AF:

0.0436

AC:

210

AN:

4816

European-Finnish (FIN)

AF:

0.0277

AC:

294

AN:

10606

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0384

AC:

2614

AN:

68014

Other (OTH)

AF:

0.0251

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

193

385

578

770

963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0134

Hom.:

Bravo

AF:

0.0239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

(source)

DANN

Benign

0.33

PhyloP100

-0.58

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over