22-50201341-C-T

Variant names:

• chr22-50201341-C-T
• rs753992805
• NM_031454.2:c.305C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031454.2(SELENOO):​c.305C>T​(p.Ala102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,170,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32345092).

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.305C>T	p.Ala102Val	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.305C>T	p.Ala102Val	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+173G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148836 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000587 AC: 6 AN: 1021314 Hom.: 0 Cov.: 34 AF XY: 0.00000621 AC XY: 3 AN XY: 483318

African (AFR) AF: 0.00 AC: 0 AN: 20294

American (AMR) AF: 0.00 AC: 0 AN: 6288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11402

East Asian (EAS) AF: 0.00 AC: 0 AN: 20224

South Asian (SAS) AF: 0.00 AC: 0 AN: 20046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2590

European-Non Finnish (NFE) AF: 0.00000566 AC: 5 AN: 883522

Other (OTH) AF: 0.0000257 AC: 1 AN: 38890

GnomAD4 genome AF: 0.00000672 AC: 1 AN: 148836 Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 1 AN XY: 72496

African (AFR) AF: 0.00 AC: 0 AN: 41044

American (AMR) AF: 0.00 AC: 0 AN: 14978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9320

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

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66796

Other (OTH) AF: 0.00 AC: 0 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.19
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.11
Sift	Benign	0.046	D
Sift4G	Benign	0.15	T
Polyphen		0.86	P
Vest4		0.38
MutPred		0.45		Loss of glycosylation at P101 (P = 0.0854)
MVP		0.69
MPC		0.44
ClinPred		0.98	D
GERP RS		2.9
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.39
Mutation Taster		=40/60	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: rs753992805; hg19: chr22-50639770; COSMIC: COSV100326799; COSMIC: COSV100326799;