15-101274640-G-C

Variant names:

• chr15-101274640-G-C
• rs116042612
• NM_018445.6:c.360C>G

Variant summary

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

The NM_018445.6(SELENOS):​c.360C>G​(p.Asp120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D120D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SELENOS NM_018445.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 1 publications found

Genes affected

SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a 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. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

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=0.09982994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018445.6. 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
	SELENOS	NM_018445.6	MANE Select	c.360C>G	p.Asp120Glu	missense	Exon 4 of 6	NP_060915.2
	SELENOS	NM_203472.3		c.360C>G	p.Asp120Glu	missense	Exon 4 of 7	NP_982298.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOS	ENST00000526049.6	TSL:1 MANE Select	c.360C>G	p.Asp120Glu	missense	Exon 4 of 6	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.360C>G	p.Asp120Glu	missense	Exon 4 of 7	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000528346.1	TSL:3	c.480C>G	p.Asp160Glu	missense	Exon 4 of 6	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461166 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726838

African (AFR) AF: 0.0000299 AC: 1 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111752

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
PhyloP100		0.13
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.093
Sift	Benign	0.73	T
Sift4G	Benign	0.98	T
Polyphen		0.39	B
Vest4		0.15
MutPred		0.56		Gain of helix (P = 0.062)
MVP		0.17
MPC		0.059
ClinPred		0.22	T
GERP RS		2.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.061

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

Other links and lift over

dbSNP: rs116042612; hg19: chr15-101814845;