chr22-50201299-C-T

Variant names:

• chr22-50201299-C-T
• rs1211155589
• NM_031454.2:c.263C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031454.2(SELENOO):​c.263C>T​(p.Thr88Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,100,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16861299).

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.263C>T	p.Thr88Ile	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.263C>T	p.Thr88Ile	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+215G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000743 AC: 11 AN: 148136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

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: 0.0000602

Gnomad OTH AF: 0.000489

GnomAD4 exome AF: 0.000122 AC: 116 AN: 952460 Hom.: 0 Cov.: 34 AF XY: 0.000114 AC XY: 51 AN XY: 448230

African (AFR) AF: 0.00 AC: 0 AN: 18406

American (AMR) AF: 0.000221 AC: 1 AN: 4526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9052

East Asian (EAS) AF: 0.00 AC: 0 AN: 12932

South Asian (SAS) AF: 0.00 AC: 0 AN: 18362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2278

European-Non Finnish (NFE) AF: 0.000134 AC: 113 AN: 840502

Other (OTH) AF: 0.0000578 AC: 2 AN: 34600

GnomAD4 genome AF: 0.0000742 AC: 11 AN: 148242 Hom.: 0 Cov.: 33 AF XY: 0.0000554 AC XY: 4 AN XY: 72240

African (AFR) AF: 0.0000486 AC: 2 AN: 41144

American (AMR) AF: 0.000268 AC: 4 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000602 AC: 4 AN: 66440

Other (OTH) AF: 0.000484 AC: 1 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.083	N
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.077
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.056
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.023	D
Polyphen		0.84	P
Vest4		0.093
MutPred		0.27		Loss of glycosylation at T88 (P = 0.0171)
MVP		0.53
MPC		0.43
ClinPred		0.96	D
GERP RS		0.63
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.21
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1211155589; hg19: chr22-50639728; COSMIC: COSV100327048; COSMIC: COSV100327048;