Genetic Variant SELENOO:p.Ala2Val (chr22-50201041-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031454.2(SELENOO):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,301,854 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 1 hom. )

Consequence

SELENOO
NM_031454.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

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:

TRABD-AS1 (HGNC:56049): (TRABD antisense RNA 1)

TRABD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052749217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOO	NM_031454.2 link	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 9	ENST00000380903.7	NP_113642.1	Q9BVL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOO	ENST00000380903.7 link	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 9	1	NM_031454.2	ENSP00000370288.2		Q9BVL4
TRABD-AS1	ENST00000608025.2 link	n.-204G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000689

AC:

104

AN:

150934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000396

AC:

AN:

25246

Hom.:

AF XY:

0.0000640

AC XY:

AN XY:

15622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000878

AC:

101

AN:

1150814

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

558064

show subpopulations

Gnomad4 AFR exome

AF:

0.00277

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000379

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.000695

AC:

105

AN:

151040

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

AN XY:

73826

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.000460

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000831

ExAC

AF:

0.0000231

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the SELO gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.16

.;N

REVEL

Benign

0.058

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.70

T;T

Polyphen

0.062

.;B

Vest4

0.41

MVP

0.24

MPC

0.095

ClinPred

0.22

GERP RS

1.6

Varity_R

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over