15-101274640-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018445.6(SELENOS):​c.360C>T​(p.Asp120Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,613,504 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (5 hom.)
• Consequence: SELENOS NM_018445.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 15-101274640-G-A is Benign according to our data. Variant chr15-101274640-G-A is described in ClinVar as Benign. ClinVar VariationId is 783723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.134 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00507 (773/152342) while in subpopulation AFR AF = 0.0178 (739/41564). AF 95% confidence interval is 0.0167. There are 11 homozygotes in GnomAd4. There are 371 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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>T	p.Asp120Asp	synonymous	Exon 4 of 6	NP_060915.2
	SELENOS	NM_203472.3		c.360C>T	p.Asp120Asp	synonymous	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>T	p.Asp120Asp	synonymous	Exon 4 of 6	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.360C>T	p.Asp120Asp	synonymous	Exon 4 of 7	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000528346.1	TSL:3	c.480C>T	p.Asp160Asp	synonymous	Exon 4 of 6	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes AF: 0.00499 AC: 760 AN: 152224 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00114 AC: 283 AN: 248406 AF XY: 0.000935

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000524 AC: 765 AN: 1461162 Hom.: 5 Cov.: 31 AF XY: 0.000443 AC XY: 322 AN XY: 726836

African (AFR) AF: 0.0168 AC: 562 AN: 33428

American (AMR) AF: 0.00112 AC: 50 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: 0.0000929 AC: 8 AN: 86104

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

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111752

Other (OTH) AF: 0.00152 AC: 92 AN: 60348

GnomAD4 genome AF: 0.00507 AC: 773 AN: 152342 Hom.: 11 Cov.: 33 AF XY: 0.00498 AC XY: 371 AN XY: 74494

African (AFR) AF: 0.0178 AC: 739 AN: 41564

American (AMR) AF: 0.00150 AC: 23 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00156 Hom.: 0

Bravo AF: 0.00575

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.9
DANN	Benign	0.57
PhyloP100		0.13
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;