chr22-50201385-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/17 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOO	NM_031454.2	c.349G>C	p.Glu117Gln	missense_variant	Exon 1 of 9	ENST00000380903.7	NP_113642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOO	ENST00000380903.7	c.349G>C	p.Glu117Gln	missense_variant	Exon 1 of 9	1	NM_031454.2	ENSP00000370288.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349G>C (p.E117Q) alteration is located in exon 1 (coding exon 1) of the SELO gene. This alteration results from a G to C substitution at nucleotide position 349, causing the glutamic acid (E) at amino acid position 117 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.64	.;N
REVEL	Benign	0.088
Sift	Benign	0.17	.;T
Sift4G	Benign	0.20	T;T
Polyphen		0.18	.;B
Vest4		0.083
MutPred		0.24		Loss of disorder (P = 0.1868);Loss of disorder (P = 0.1868);
MVP		0.27
MPC		0.17
ClinPred		0.40	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50639814;