Genetic Variant ENST00000398226.8: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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new If you want to explore the variant's impact on the transcript ENST00000398226.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398226.8. 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_203472.3		c.*571G>C		3_prime_UTR	Exon 7 of 7	NP_982298.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOS	ENST00000398226.8	TSL:1	c.*565G>C		3_prime_UTR	Exon 7 of 7	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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over