5-42801166-C-T

Position:

• chr5-42801166-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOP	NM_005410.4	c.700G>A	p.Ala234Thr	missense_variant	5/5	ENST00000514985.6
CCDC152	NM_001134848.2	c.*1385C>T		3_prime_UTR_variant	9/9	ENST00000361970.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOP	ENST00000514985.6	c.700G>A	p.Ala234Thr	missense_variant	5/5	1	NM_005410.4	P1
CCDC152	ENST00000361970.10	c.*1385C>T		3_prime_UTR_variant	9/9	1	NM_001134848.2	P1

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

GnomAD3 exomes AF: 0.201 AC: 49686 AN: 247196 Hom.: 5896 AF XY: 0.202 AC XY: 27132 AN XY: 134328

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 SAS exome AF: 0.131

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

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.226

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

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.245

Alfa AF: 0.233 Hom.: 9529

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 v4.3

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;T;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.13	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.82	T;T;T;T
Sift4G	Benign	0.43	T;T;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

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