rs760598

Positions:

chr1-25811645-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020451.3(SELENON):c.1093-46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 1,608,850 control chromosomes in the GnomAD database, including 481,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38906 hom., cov: 32)

Exomes 𝑓: 0.78 ( 442108 hom. )

Consequence

SELENON
NM_020451.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.911

Variant links:

Genes affected

SELENON (HGNC:15999): (selenoprotein N) This gene encodes a glycoprotein that is localized in the endoplasmic reticulum. It plays an important role in cell protection against oxidative stress, and in the regulation of redox-related calcium homeostasis. Mutations in this gene are associated with early onset muscle disorders, referred to as SEPN1-related myopathy. SEPN1-related myopathy consists of 4 autosomal recessive disorders, originally thought to be separate entities: rigid spine muscular dystrophy (RSMD1), the classical form of multiminicore disease, desmin related myopathy with Mallory-body like inclusions, and congenital fiber-type disproportion (CFTD). 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. A second stop-codon redefinition element (SRE) adjacent to the UGA codon has been identified in this gene (PMID:15791204). SRE is a phylogenetically conserved stem-loop structure that stimulates readthrough at the UGA codon, and augments the Sec insertion efficiency by SECIS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2016]

SELENON links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-25811645-C-A is Benign according to our data. Variant chr1-25811645-C-A is described in ClinVar as [Benign]. Clinvar id is 261271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-25811645-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENON	NM_020451.3 linkuse as main transcript	c.1093-46C>A		intron_variant		ENST00000361547.7	NP_065184.2
SELENON	NM_206926.2 linkuse as main transcript	c.991-46C>A		intron_variant			NP_996809.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SELENON	ENST00000361547.7 linkuse as main transcript	c.1093-46C>A	intron_variant	1	NM_020451.3	ENSP00000355141		Q9NZV5-1
SELENON	ENST00000354177.9 linkuse as main transcript	c.922-46C>A	intron_variant	5		ENSP00000346109
SELENON	ENST00000374315.1 linkuse as main transcript	c.991-46C>A	intron_variant	5		ENSP00000363434	P1	Q9NZV5-2
SELENON	ENST00000494537.2 linkuse as main transcript	c.991-46C>A	intron_variant, NMD_transcript_variant	3		ENSP00000508308

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106247

AN:

151984

Hom.:

38885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.931

Gnomad AMR

AF:

0.804

Gnomad ASJ

AF:

0.760

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.886

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.726

GnomAD3 exomes

AF:

0.790

AC:

194529

AN:

246134

Hom.:

78350

AF XY:

0.795

AC XY:

106372

AN XY:

133820

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.880

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.965

Gnomad SAS exome

AF:

0.874

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.768

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.776

AC:

1130371

AN:

1456748

Hom.:

442108

Cov.:

AF XY:

0.780

AC XY:

565250

AN XY:

724996

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.873

Gnomad4 ASJ exome

AF:

0.763

Gnomad4 EAS exome

AF:

0.961

Gnomad4 SAS exome

AF:

0.875

Gnomad4 FIN exome

AF:

0.743

Gnomad4 NFE exome

AF:

0.769

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.699

AC:

106303

AN:

152102

Hom.:

38906

Cov.:

AF XY:

0.705

AC XY:

52430

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.805

Gnomad4 ASJ

AF:

0.760

Gnomad4 EAS

AF:

0.966

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.765

Hom.:

46030

Bravo

AF:

0.694

Asia WGS

AF:

0.893

AC:

3108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Eichsfeld type congenital muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.3

DANN

Benign

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over