Genetic Variant SELENOO:p.Pro40Thr (chr22-50201154-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031454.2(SELENOO):c.118C>A(p.Pro40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SELENOO
NM_031454.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

Publications

0 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:

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

TRABD-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07854402).

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.118C>A	p.Pro40Thr	missense	Exon 1 of 9	NP_113642.1	Q9BVL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOO	ENST00000380903.7	TSL:1 MANE Select	c.118C>A	p.Pro40Thr	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+360G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1111206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

533164

African (AFR)

AF:

0.00

AC:

AN:

22332

American (AMR)

AF:

0.00

AC:

AN:

8938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15108

East Asian (EAS)

AF:

0.00

AC:

AN:

25694

South Asian (SAS)

AF:

0.00

AC:

AN:

32204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

936700

Other (OTH)

AF:

0.00

AC:

AN:

44032

GnomAD4 genome

Cov.:

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

Benign

0.073

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.014

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.50

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PhyloP100

-3.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.32

REVEL

Benign

0.014

Sift

Benign

0.15

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.070

MutPred

0.22

Gain of MoRF binding (P = 0.0435)

MVP

0.24

MPC

0.11

ClinPred

0.062

GERP RS

-0.37

PromoterAI

-0.28

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.056

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over