1-25811771-T-C

Position:

chr1-25811771-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020451.3(SELENON):c.1173T>C(p.Pro391Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,592,998 control chromosomes in the GnomAD database, including 499,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43500 hom., cov: 34)

Exomes 𝑓: 0.79 ( 456466 hom. )

Consequence

SELENON
NM_020451.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.302

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:

ENSG00000255054 (HGNC:):

ENSG00000255054 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 1-25811771-T-C is Benign according to our data. Variant chr1-25811771-T-C is described in ClinVar as [Benign]. Clinvar id is 95956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-25811771-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.302 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 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.1173T>C	p.Pro391Pro	synonymous_variant	9/13	ENST00000361547.7	NP_065184.2	Q9NZV5-1
SELENON	NM_206926.2 linkuse as main transcript	c.1071T>C	p.Pro357Pro	synonymous_variant	8/12		NP_996809.1	Q9NZV5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENON	ENST00000361547.7 linkuse as main transcript	c.1173T>C	p.Pro391Pro	synonymous_variant	9/13	1	NM_020451.3	ENSP00000355141.2		Q9NZV5-1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113974

AN:

152086

Hom.:

43465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.781

Gnomad OTH

AF:

0.759

GnomAD3 exomes

AF:

0.810

AC:

171867

AN:

212212

Hom.:

70251

AF XY:

0.812

AC XY:

93414

AN XY:

115030

show subpopulations

Gnomad AFR exome

AF:

0.607

Gnomad AMR exome

AF:

0.891

Gnomad ASJ exome

AF:

0.771

Gnomad EAS exome

AF:

0.965

Gnomad SAS exome

AF:

0.877

Gnomad FIN exome

AF:

0.741

Gnomad NFE exome

AF:

0.784

Gnomad OTH exome

AF:

0.811

GnomAD4 exome

AF:

0.794

AC:

1144177

AN:

1440794

Hom.:

456466

Cov.:

AF XY:

0.797

AC XY:

569704

AN XY:

714946

show subpopulations

Gnomad4 AFR exome

AF:

0.606

Gnomad4 AMR exome

AF:

0.884

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.960

Gnomad4 SAS exome

AF:

0.878

Gnomad4 FIN exome

AF:

0.744

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.794

GnomAD4 genome

AF:

0.749

AC:

114063

AN:

152204

Hom.:

43500

Cov.:

AF XY:

0.753

AC XY:

56067

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.765

Gnomad4 EAS

AF:

0.966

Gnomad4 SAS

AF:

0.887

Gnomad4 FIN

AF:

0.755

Gnomad4 NFE

AF:

0.781

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.767

Hom.:

28216

Bravo

AF:

0.750

Asia WGS

AF:

0.907

AC:

3152

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 07, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	This is a RefSeq error. The reference base (c.1173T) is the minor allele. This a llele (T) has been identified in 21% (1788/8438) of European American chromosome s and 37% (1521/4152) of African American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs760597) and thus meets c riteria to be classified as benign. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Eichsfeld type congenital muscular dystrophy

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 18, 2018	- -

SEPN1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.2

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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