chr5-42801166-C-T

Variant names:

• chr5-42801166-C-T
• rs3877899
• NM_005410.4:c.700G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005410.4(SELENOP):​c.700G>A​(p.Ala234Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,784 control chromosomes in the GnomAD database, including 44,356 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4469 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39887 hom.)
• Consequence: SELENOP NM_005410.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 96 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043133795).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

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.700G>A	p.Ala234Thr	missense	Exon 5 of 5	NP_005401.3
	CCDC152	NM_001134848.2	MANE Select	c.*1385C>T		3_prime_UTR	Exon 9 of 9	NP_001128320.1	Q4G0S7-1
	SELENOP	NM_001093726.3		c.790G>A	p.Ala264Thr	missense	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.700G>A	p.Ala234Thr	missense	Exon 5 of 5	ENSP00000420939.1	P49908
	SELENOP	ENST00000506577.5	TSL:1	c.700G>A	p.Ala234Thr	missense	Exon 5 of 5	ENSP00000425915.1	P49908
	SELENOP	ENST00000511224.5	TSL:1	c.700G>A	p.Ala234Thr	missense	Exon 6 of 6	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35543 AN: 151846 Hom.: 4470 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.201 AC: 49686 AN: 247196 AF XY: 0.202

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.265

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.227 AC: 331229 AN: 1461820 Hom.: 39887 Cov.: 36 AF XY: 0.224 AC XY: 163188 AN XY: 727214

African (AFR) AF: 0.268 AC: 8965 AN: 33476

American (AMR) AF: 0.143 AC: 6375 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6774 AN: 26136

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39700

South Asian (SAS) AF: 0.133 AC: 11464 AN: 86256

European-Finnish (FIN) AF: 0.285 AC: 15220 AN: 53420

Middle Eastern (MID) AF: 0.236 AC: 1362 AN: 5768

European-Non Finnish (NFE) AF: 0.240 AC: 267395 AN: 1111950

Other (OTH) AF: 0.226 AC: 13660 AN: 60390

GnomAD4 genome AF: 0.234 AC: 35561 AN: 151964 Hom.: 4469 Cov.: 32 AF XY: 0.230 AC XY: 17108 AN XY: 74274

African (AFR) AF: 0.267 AC: 11041 AN: 41426

American (AMR) AF: 0.187 AC: 2864 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.122 AC: 583 AN: 4794

European-Finnish (FIN) AF: 0.286 AC: 3014 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16248 AN: 67958

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.232 Hom.: 14651

Bravo AF: 0.231

TwinsUK AF: 0.243 AC: 901

ALSPAC AF: 0.245 AC: 945

ESP6500AA AF: 0.249 AC: 1064

ESP6500EA AF: 0.234 AC: 1988

ExAC AF: 0.202 AC: 24413

Asia WGS AF: 0.0640 AC: 225 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.7
DANN	Benign	0.83
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.84
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.050
Sift	Benign	0.82	T
Sift4G	Benign	0.43	T
MPC		0.29
ClinPred		0.015	T
GERP RS		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
Mutation Taster		=100/0	polymorphism (auto)

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: rs3877899; hg19: chr5-42801268; COSMIC: COSV62792555; COSMIC: COSV62792555;