NM_031454.2:c.349G>C

Variant names:

• chr22-50201385-G-C
• rs1395457778
• NM_031454.2:c.349G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031454.2(SELENOO):​c.349G>C​(p.Glu117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000905 in 1,104,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.163932).

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.349G>C	p.Glu117Gln	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.349G>C	p.Glu117Gln	missense	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+129C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 9.05e-7 AC: 1 AN: 1104900 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 531724

African (AFR) AF: 0.00 AC: 0 AN: 22020

American (AMR) AF: 0.00 AC: 0 AN: 8918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14194

East Asian (EAS) AF: 0.00 AC: 0 AN: 24032

South Asian (SAS) AF: 0.00 AC: 0 AN: 34474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2940

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 931616

Other (OTH) AF: 0.00 AC: 0 AN: 43220

GnomAD4 genome Cov.: 35

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	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.26
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.088
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.18	B
Vest4		0.083
MutPred		0.24		Loss of disorder (P = 0.1868)
MVP		0.27
MPC		0.17
ClinPred		0.40	T
GERP RS		3.3
PromoterAI		0.090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
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: rs1395457778; hg19: chr22-50639814;