NM_031454.2:c.26G>A

Variant names:

• chr22-50201062-G-A
• rs1472744659
• NM_031454.2:c.26G>A

Variant summary

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

The NM_031454.2(SELENOO):​c.26G>A​(p.Gly9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,357,398 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.617
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14330149).

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.26G>A	p.Gly9Glu	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.26G>A	p.Gly9Glu	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+452C>T		intron	N/A
	TRABD-AS1	ENST00000608025.3	TSL:2	n.-225C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151854 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000479

GnomAD2 exomes AF: 0.00 AC: 0 AN: 42302 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 16 AN: 1205544 Hom.: 0 Cov.: 35 AF XY: 0.0000119 AC XY: 7 AN XY: 590446

African (AFR) AF: 0.000460 AC: 11 AN: 23922

American (AMR) AF: 0.0000624 AC: 1 AN: 16038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19508

East Asian (EAS) AF: 0.00 AC: 0 AN: 27064

South Asian (SAS) AF: 0.00 AC: 0 AN: 51868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3474

European-Non Finnish (NFE) AF: 0.00000405 AC: 4 AN: 987554

Other (OTH) AF: 0.00 AC: 0 AN: 48290

GnomAD4 genome AF: 0.000171 AC: 26 AN: 151854 Hom.: 1 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74178

African (AFR) AF: 0.000507 AC: 21 AN: 41382

American (AMR) AF: 0.000262 AC: 4 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67890

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000208

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	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.62
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.086
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.38		Loss of MoRF binding (P = 0.0577)
MVP		0.33
MPC		0.13
ClinPred		0.17	T
GERP RS		1.9
PromoterAI		-0.034	Neutral
Varity_R		0.16
Mutation Taster		=99/1	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: rs1472744659; hg19: chr22-50639491;