rs10902685

Positions:

chr1-25812646-C-T

Variant summary

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

The NM_020451.3(SELENON):c.1282-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,525,118 control chromosomes in the GnomAD database, including 467,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 36519 hom., cov: 25)

Exomes 𝑓: 0.79 ( 430938 hom. )

Consequence

SELENON
NM_020451.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0280

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=-0.84).

BP6

Variant 1-25812646-C-T is Benign according to our data. Variant chr1-25812646-C-T is described in ClinVar as [Benign]. Clinvar id is 261274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-25812646-C-T is described in Lovd as [Benign].

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.1282-41C>T		intron_variant		ENST00000361547.7	NP_065184.2
SELENON	NM_206926.2 linkuse as main transcript	c.1180-41C>T		intron_variant			NP_996809.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SELENON	ENST00000361547.7 linkuse as main transcript	c.1282-41C>T	intron_variant	1	NM_020451.3	ENSP00000355141		Q9NZV5-1
SELENON	ENST00000354177.9 linkuse as main transcript	c.1111-41C>T	intron_variant	5		ENSP00000346109
SELENON	ENST00000374315.1 linkuse as main transcript	c.1180-41C>T	intron_variant	5		ENSP00000363434	P1	Q9NZV5-2
SELENON	ENST00000494537.2 linkuse as main transcript	c.1180-41C>T	intron_variant, NMD_transcript_variant	3		ENSP00000508308

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

98897

AN:

150196

Hom.:

36507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.938

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.766

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.886

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.793

AC:

166235

AN:

209640

Hom.:

67996

AF XY:

0.800

AC XY:

91013

AN XY:

113744

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.879

Gnomad ASJ exome

AF:

0.773

Gnomad EAS exome

AF:

0.966

Gnomad SAS exome

AF:

0.878

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.787

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.786

AC:

1080867

AN:

1374802

Hom.:

430938

Cov.:

AF XY:

0.790

AC XY:

541910

AN XY:

685702

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.869

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.961

Gnomad4 SAS exome

AF:

0.879

Gnomad4 FIN exome

AF:

0.745

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.774

GnomAD4 genome

AF:

0.658

AC:

98932

AN:

150316

Hom.:

36519

Cov.:

AF XY:

0.664

AC XY:

48651

AN XY:

73240

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.766

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.780

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.725

Hom.:

7763

Bravo

AF:

0.647

Asia WGS

AF:

0.883

AC:

3067

AN:

3474

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

-0.84

CADD

Benign

1.2

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.98

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