rs750577534

Variant names:

• chr22-50201388-G-T
• rs750577534
• NM_031454.2:c.352G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50201388-G-T
• chr22-50201388-G-A
• chr22-50201388-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031454.2(SELENOO):​c.352G>T​(p.Ala118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000729 in 1,274,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00032 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013492525).

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.352G>T	p.Ala118Ser	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.352G>T	p.Ala118Ser	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+126C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000319 AC: 48 AN: 150400 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.00117

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000649 AC: 1 AN: 15408 AF XY: 0.00

Gnomad AFR exome AF: 0.00352

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: 0.0000400 AC: 45 AN: 1124466 Hom.: 0 Cov.: 37 AF XY: 0.0000387 AC XY: 21 AN XY: 543190

African (AFR) AF: 0.00169 AC: 38 AN: 22490

American (AMR) AF: 0.00 AC: 0 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14908

East Asian (EAS) AF: 0.00 AC: 0 AN: 24292

South Asian (SAS) AF: 0.00 AC: 0 AN: 39516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3020

European-Non Finnish (NFE) AF: 0.00000638 AC: 6 AN: 940940

Other (OTH) AF: 0.0000227 AC: 1 AN: 44130

GnomAD4 genome AF: 0.000319 AC: 48 AN: 150508 Hom.: 0 Cov.: 35 AF XY: 0.000272 AC XY: 20 AN XY: 73488

African (AFR) AF: 0.00116 AC: 48 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67462

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000272

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	0.11
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.33	N
REVEL	Benign	0.059
Sift	Benign	0.76	T
Sift4G	Benign	0.75	T
Polyphen		0.082	B
Vest4		0.091
MutPred		0.40		Gain of glycosylation at A118 (P = 0.0185)
MVP		0.38
MPC		0.10
ClinPred		0.17	T
GERP RS		3.3
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.13
Mutation Taster		=85/15	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: rs750577534; hg19: chr22-50639817;