Variant 5-42808299-T-TC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_005410.4(SELENOP):c.54_55insG(p.Thr19AspfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,531,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

SELENOP
NM_005410.4 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0190

Variant links:

Genes affected

SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. 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. The mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]

SELENOP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 5-42808299-T-TC is Benign according to our data. Variant chr5-42808299-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 747158.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SELENOP	NM_005410.4 linkuse as main transcript	c.54_55insG	p.Thr19AspfsTer11	frameshift_variant	2/5	ENST00000514985.6
SELENOP	NM_001085486.3 linkuse as main transcript	c.54_55insG	p.Thr19AspfsTer11	frameshift_variant	3/6
SELENOP	NM_001093726.3 linkuse as main transcript	c.144_145insG	p.Thr49AspfsTer11	frameshift_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOP	ENST00000514985.6 linkuse as main transcript	c.54_55insG	p.Thr19AspfsTer11	frameshift_variant	2/5	1	NM_005410.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000317

AC:

AN:

195522

Hom.:

AF XY:

0.000336

AC XY:

AN XY:

107214

show subpopulations

Gnomad AFR exome

AF:

0.000163

Gnomad AMR exome

AF:

0.000635

Gnomad ASJ exome

AF:

0.00207

Gnomad EAS exome

AF:

0.000162

Gnomad SAS exome

AF:

0.000137

Gnomad FIN exome

AF:

0.000587

Gnomad NFE exome

AF:

0.0000953

Gnomad OTH exome

AF:

0.000928

GnomAD4 exome

AF:

0.000304

AC:

420

AN:

1380022

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

194

AN XY:

685714

show subpopulations

Gnomad4 AFR exome

AF:

0.000170

Gnomad4 AMR exome

AF:

0.000606

Gnomad4 ASJ exome

AF:

0.00268

Gnomad4 EAS exome

AF:

0.000308

Gnomad4 SAS exome

AF:

0.000190

Gnomad4 FIN exome

AF:

0.000406

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.000534

GnomAD4 genome

AF:

0.000217

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.000868

Gnomad4 EAS

AF:

0.000394

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000473

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000436

Hom.:

Bravo

AF:

0.000257

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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