Variant 1-25808435-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020451.3(SELENON):c.538-145C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 872,964 control chromosomes in the GnomAD database, including 27,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3774 hom., cov: 32)

Exomes 𝑓: 0.25 ( 23826 hom. )

Consequence

SELENON
NM_020451.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.60

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-25808435-C-G is Benign according to our data. Variant chr1-25808435-C-G is described in ClinVar as [Benign]. Clinvar id is 1262044.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 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.538-145C>G		intron_variant		ENST00000361547.7	NP_065184.2	Q9NZV5-1
SELENON	NM_206926.2 linkuse as main transcript	c.436-145C>G		intron_variant			NP_996809.1	Q9NZV5-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SELENON	ENST00000361547.7 linkuse as main transcript	c.538-145C>G	intron_variant	1	NM_020451.3	ENSP00000355141.2	Q9NZV5-1
SELENON	ENST00000374315.1 linkuse as main transcript	c.436-145C>G	intron_variant	5		ENSP00000363434.1	Q9NZV5-2
SELENON	ENST00000354177.9 linkuse as main transcript	c.436-145C>G	intron_variant	5		ENSP00000346109.5	H9KV50
SELENON	ENST00000494537.2 linkuse as main transcript	n.436-145C>G	intron_variant	3		ENSP00000508308.1	A0A804HLD6

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30583

AN:

152014

Hom.:

3773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.249

AC:

179744

AN:

720832

Hom.:

23826

AF XY:

0.246

AC XY:

92538

AN XY:

375758

show subpopulations

Gnomad4 AFR exome

AF:

0.0583

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.371

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.201

AC:

30572

AN:

152132

Hom.:

3774

Cov.:

AF XY:

0.202

AC XY:

15010

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0620

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.125

Hom.:

242

Bravo

AF:

0.198

Asia WGS

AF:

0.185

AC:

634

AN:

3444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.056

DANN

Benign

0.39

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