22-50208712-G-C

Variant names:

• chr22-50208712-G-C
• rs780144198
• NM_031454.2:c.935G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031454.2(SELENOO):​c.935G>C​(p.Arg312Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R312Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• 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]

SELENOO-AS1 (HGNC:56048): (SELENOO antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

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.935G>C	p.Arg312Pro	missense	Exon 3 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.935G>C	p.Arg312Pro	missense	Exon 3 of 9	ENSP00000370288.2	Q9BVL4
	SELENOO	ENST00000492092.1	TSL:1	n.304G>C		non_coding_transcript_exon	Exon 2 of 8
	SELENOO-AS1	ENST00000608016.1	TSL:3	n.389C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		3.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.27
Sift	Benign	0.053	T
Sift4G	Benign	0.11	T
Polyphen		0.021	B
Vest4		0.60
MutPred		0.74		Loss of MoRF binding (P = 0.001)
MVP		0.58
MPC		0.16
ClinPred		0.39	T
GERP RS		2.1
Varity_R		0.96
Mutation Taster		=79/21	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: rs780144198; hg19: chr22-50647141;