22-50201296-C-G

Variant names:

• chr22-50201296-C-G
• rs1485591090
• NM_031454.2:c.260C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031454.2(SELENOO):​c.260C>G​(p.Pro87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,096,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.260C>G	p.Pro87Arg	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.260C>G	p.Pro87Arg	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+218G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000203 AC: 3 AN: 148036 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

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: 0.00

GnomAD4 exome AF: 0.00000316 AC: 3 AN: 948028 Hom.: 0 Cov.: 33 AF XY: 0.00000224 AC XY: 1 AN XY: 446152

African (AFR) AF: 0.00 AC: 0 AN: 18294

American (AMR) AF: 0.00 AC: 0 AN: 4432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8904

East Asian (EAS) AF: 0.00 AC: 0 AN: 12382

South Asian (SAS) AF: 0.00 AC: 0 AN: 18324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2260

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 837706

Other (OTH) AF: 0.0000291 AC: 1 AN: 34318

GnomAD4 genome AF: 0.0000203 AC: 3 AN: 148146 Hom.: 0 Cov.: 33 AF XY: 0.0000415 AC XY: 3 AN XY: 72214

African (AFR) AF: 0.00 AC: 0 AN: 41138

American (AMR) AF: 0.000201 AC: 3 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9054

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66404

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	4.4	H
PhyloP100		2.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.56		Gain of MoRF binding (P = 4e-04)
MVP		0.75
MPC		0.52
ClinPred		1.0	D
GERP RS		2.9
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.92
Mutation Taster		=32/68	disease causing

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: rs1485591090; hg19: chr22-50639725;