Genetic Variant SELENOO:p.Glu294Lys (chr22-50208657-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_031454.2(SELENOO):c.880G>A(p.Glu294Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,613,758 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 19 hom. )

Consequence

SELENOO
NM_031454.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 9.86

Publications

8 publications found

Variant links:

Genes affected

SELENOO (HGNC:30395): (selenoprotein O) This gene encodes a selenoprotein that is localized to the mitochondria. It is the largest mammalian 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. The exact function of this selenoprotein is not known, but it is thought to have redox activity. [provided by RefSeq, Dec 2016]

SELENOO links:

SELENOO-AS1 (HGNC:56048): (SELENOO antisense RNA 1)

SELENOO-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012123585).

BP6

Variant 22-50208657-G-A is Benign according to our data. Variant chr22-50208657-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2653368.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031454.2. 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
	SELENOO	NM_031454.2	MANE Select	c.880G>A	p.Glu294Lys	missense	Exon 3 of 9	NP_113642.1	Q9BVL4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SELENOO	ENST00000380903.7	TSL:1 MANE Select	c.880G>A	p.Glu294Lys	missense	Exon 3 of 9	ENSP00000370288.2	Q9BVL4
SELENOO	ENST00000492092.1	TSL:1	n.249G>A		non_coding_transcript_exon	Exon 2 of 8
SELENOO-AS1	ENST00000608016.1	TSL:3	n.444C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00278

AC:

423

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00406

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00286

AC:

713

AN:

249328

AF XY:

0.00295

show subpopulations

Gnomad AFR exome

AF:

0.000905

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000698

Gnomad NFE exome

AF:

0.00373

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00340

AC:

4969

AN:

1461458

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2473

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.000806

AC:

AN:

33480

American (AMR)

AF:

0.00349

AC:

156

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00712

AC:

186

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00112

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000924

AC:

AN:

53030

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00379

AC:

4216

AN:

1111980

Other (OTH)

AF:

0.00349

AC:

211

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.00278

AC:

423

AN:

152300

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41560

American (AMR)

AF:

0.00392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000470

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00406

AC:

276

AN:

68006

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

114

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:

0.00384

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000719

AC:

ESP6500EA

AF:

0.00415

AC:

ExAC

AF:

0.00256

AC:

310

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00425

EpiControl

AF:

0.00427

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.4

PhyloP100

9.9

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.33

Sift

Benign

0.056

Sift4G

Benign

0.11

Polyphen

0.90

Vest4

0.72

MVP

0.69

MPC

0.18

ClinPred

0.045

GERP RS

5.3

Varity_R

0.47

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over