5-42808299-T-TC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190

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]

ACMG classification

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	UniProt
SELENOP	NM_005410.4	c.54_55insG	p.Thr19AspfsTer11	frameshift_variant	2/5	ENST00000514985.6
SELENOP	NM_001085486.3	c.54_55insG	p.Thr19AspfsTer11	frameshift_variant	3/6
SELENOP	NM_001093726.3	c.144_145insG	p.Thr49AspfsTer11	frameshift_variant	3/6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151656 Hom.: 0 Cov.: 31

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: 62 AN: 195522 Hom.: 0 AF XY: 0.000336 AC XY: 36 AN XY: 107214

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.: 0 Cov.: 28 AF XY: 0.000283 AC XY: 194 AN XY: 685714

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: 33 AN: 151778 Hom.: 0 Cov.: 31 AF XY: 0.000189 AC XY: 14 AN XY: 74216

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.: 0

Bravo AF: 0.000257

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs745867439; hg19: chr5-42808401;