rs369461259

Variant names:

• chr22-50208700-C-G
• rs369461259
• NM_031454.2:c.923C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50208700-C-G
• chr22-50208700-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031454.2(SELENOO):​c.923C>G​(p.Ala308Gly) 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 benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SELENOO NM_031454.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42340955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOO	NM_031454.2	c.923C>G	p.Ala308Gly	missense_variant	Exon 3 of 9	ENST00000380903.7	NP_113642.1
SELENOO-AS1	XR_938352.3	n.1040G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOO	ENST00000380903.7	c.923C>G	p.Ala308Gly	missense_variant	Exon 3 of 9	1	NM_031454.2	ENSP00000370288.2
SELENOO	ENST00000492092.1	n.292C>G		non_coding_transcript_exon_variant	Exon 2 of 8	1
SELENOO-AS1	ENST00000608016.1	n.401G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248624 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135026

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.90	D;D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.15
Sift	Benign	0.11	.;T
Sift4G	Uncertain	0.052	T;T
Polyphen		0.080	.;B
Vest4		0.59
MutPred		0.57		Gain of disorder (P = 0.1267);Gain of disorder (P = 0.1267);
MVP		0.37
MPC		0.24
ClinPred		0.16	T
GERP RS		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369461259; hg19: chr22-50647129;