15-101274611-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018445.6(SELENOS):c.389G>T(p.Gly130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,613,562 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (155 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (144 hom.)
• Consequence: SELENOS NM_018445.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.32

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-101274611-C-A is Benign according to our data. Variant chr15-101274611-C-A is described in ClinVar as [Benign]. Clinvar id is 776948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOS	NM_018445.6	c.389G>T	p.Gly130Val	missense_variant	4/6	ENST00000526049.6
SELENOS	NM_203472.3	c.389G>T	p.Gly130Val	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOS	ENST00000526049.6	c.389G>T	p.Gly130Val	missense_variant	4/6	1	NM_018445.6	P1

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4066 AN: 152184 Hom.: 155 Cov.: 33

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.00751 AC: 1865 AN: 248400 Hom.: 62 AF XY: 0.00641 AC XY: 864 AN XY: 134782

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.00687

Gnomad ASJ exome AF: 0.000896

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.000820

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.00763

GnomAD4 exome AF: 0.00388 AC: 5665 AN: 1461260 Hom.: 144 Cov.: 31 AF XY: 0.00366 AC XY: 2659 AN XY: 726896

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.00809

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000963

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.00868

GnomAD4 genome AF: 0.0267 AC: 4070 AN: 152302 Hom.: 155 Cov.: 33 AF XY: 0.0264 AC XY: 1963 AN XY: 74470

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.00644 Hom.: 50

Bravo AF: 0.0296

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.0722 AC: 272

ESP6500EA AF: 0.00122 AC: 10

ExAC AF: 0.00842 AC: 1017

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.054
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.20	T;T;T;.
Polyphen		0.15	B;.;B;.
Vest4		0.28
MVP		0.34
MPC		0.073
ClinPred		0.025	T
GERP RS		4.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs79140824; hg19: chr15-101814816;