5-42800733-C-T

Variant names:

• chr5-42800733-C-T
• rs940762037
• NM_005410.4:c.1133G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005410.4(SELENOP):​c.1133G>A​(p.Ter378Ter) variant causes a stop retained change. The variant allele was found at a frequency of 0.00000499 in 1,603,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SELENOP NM_005410.4 stop_retained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12
• Publications: 0 publications found

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]

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.127176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005410.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	NM_005410.4	MANE Select	c.1133G>A	p.Ter378Ter	stop_retained	Exon 5 of 5	NP_005401.3
	CCDC152	NM_001134848.2	MANE Select	c.*952C>T		3_prime_UTR	Exon 9 of 9	NP_001128320.1	Q4G0S7-1
	SELENOP	NM_001093726.3		c.1223G>A	p.Ter408Ter	stop_retained	Exon 6 of 6	NP_001087195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.1133G>A	p.Ter378Ter	stop_retained	Exon 5 of 5	ENSP00000420939.1	P49908
	SELENOP	ENST00000506577.5	TSL:1	c.1133G>A	p.Ter378Ter	stop_retained	Exon 5 of 5	ENSP00000425915.1	P49908
	SELENOP	ENST00000511224.5	TSL:1	c.1133G>A	p.Ter378Ter	stop_retained	Exon 6 of 6	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1451798 Hom.: 0 Cov.: 32 AF XY: 0.00000417 AC XY: 3 AN XY: 720156

African (AFR) AF: 0.00 AC: 0 AN: 33196

American (AMR) AF: 0.00 AC: 0 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 85376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1104728

Other (OTH) AF: 0.0000334 AC: 2 AN: 59932

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	38
DANN	Benign	0.86
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		6.1
GERP RS		5.8
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs940762037; hg19: chr5-42800835;