rs187960531

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020451.3(SELENON):c.42C>T(p.Pro14Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 971,178 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 105 hom., cov: 30)

Exomes 𝑓: 0.0017 ( 55 hom. )

Consequence

SELENON
NM_020451.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.588

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

rigid spine muscular dystrophy 1
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, G2P
SELENON-related myopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
congenital myopathy 4A, autosomal dominant
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
desmin-related myopathy with Mallory body-like inclusions
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
rigid spine syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SELENON links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-25800272-C-T is Benign according to our data. Variant chr1-25800272-C-T is described in ClinVar as Benign. ClinVar VariationId is 95964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENON	NM_020451.3 link	c.42C>T	p.Pro14Pro	synonymous_variant	Exon 1 of 13	ENST00000361547.7	NP_065184.2
SELENON	NM_206926.2 link	c.42C>T	p.Pro14Pro	synonymous_variant	Exon 1 of 12		NP_996809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SELENON	ENST00000361547.7 link	c.42C>T	p.Pro14Pro	synonymous_variant	Exon 1 of 13	1	NM_020451.3	ENSP00000355141.2
SELENON	ENST00000374315.1 link	c.42C>T	p.Pro14Pro	synonymous_variant	Exon 1 of 12	5		ENSP00000363434.1
SELENON	ENST00000354177.9 link	c.42C>T	p.Pro14Pro	synonymous_variant	Exon 1 of 12	5		ENSP00000346109.5
SELENON	ENST00000494537.2 link	n.42C>T		non_coding_transcript_exon_variant	Exon 1 of 13	3		ENSP00000508308.1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3095

AN:

146024

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00324

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.000274

Gnomad OTH

AF:

0.0114

GnomAD2 exomes

AF:

0.00433

AC:

AN:

2542

AF XY:

0.00633

show subpopulations

Gnomad AFR exome

AF:

0.0652

Gnomad AMR exome

AF:

0.00654

Gnomad ASJ exome

AF:

0.00365

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00171

AC:

1413

AN:

825096

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

650

AN XY:

382938

show subpopulations

African (AFR)

AF:

0.0753

AC:

1177

AN:

15626

American (AMR)

AF:

0.00296

AC:

AN:

1690

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

5360

East Asian (EAS)

AF:

0.00

AC:

AN:

3756

South Asian (SAS)

AF:

0.000114

AC:

AN:

17586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

466

Middle Eastern (MID)

AF:

0.00431

AC:

AN:

1624

European-Non Finnish (NFE)

AF:

0.000154

AC:

116

AN:

751968

Other (OTH)

AF:

0.00359

AC:

AN:

27020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0212

AC:

3100

AN:

146082

Hom.:

105

Cov.:

AF XY:

0.0201

AC XY:

1431

AN XY:

71066

show subpopulations

African (AFR)

AF:

0.0720

AC:

2938

AN:

40828

American (AMR)

AF:

0.00727

AC:

107

AN:

14726

Ashkenazi Jewish (ASJ)

AF:

0.00324

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8248

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000274

AC:

AN:

65770

Other (OTH)

AF:

0.0113

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0160

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 26, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SEPN1-related disorder

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Eichsfeld type congenital muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.59

PromoterAI

0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over