chr5-42800764-G-A

Position:

• chr5-42800764-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005410.4(SELENOP):​c.1102C>T​(p.Arg368Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,611,622 control chromosomes in the GnomAD database, including 30 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R368H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0026 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (26 hom.)
• Consequence: SELENOP NM_005410.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

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=0.0053276718).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00283 (4129/1459392) while in subpopulation MID AF= 0.0217 (125/5750). AF 95% confidence interval is 0.0186. There are 26 homozygotes in gnomad4_exome. There are 2182 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOP	NM_005410.4	c.1102C>T	p.Arg368Cys	missense_variant	5/5	ENST00000514985.6
CCDC152	NM_001134848.2	c.*983G>A		3_prime_UTR_variant	9/9	ENST00000361970.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOP	ENST00000514985.6	c.1102C>T	p.Arg368Cys	missense_variant	5/5	1	NM_005410.4	P1
CCDC152	ENST00000361970.10	c.*983G>A		3_prime_UTR_variant	9/9	1	NM_001134848.2	P1

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 395 AN: 152112 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00368 AC: 908 AN: 246600 Hom.: 4 AF XY: 0.00400 AC XY: 536 AN XY: 133970

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.00334

Gnomad ASJ exome AF: 0.00776

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00428

Gnomad FIN exome AF: 0.00571

Gnomad NFE exome AF: 0.00375

Gnomad OTH exome AF: 0.00647

GnomAD4 exome AF: 0.00283 AC: 4129 AN: 1459392 Hom.: 26 Cov.: 33 AF XY: 0.00301 AC XY: 2182 AN XY: 725460

Gnomad4 AFR exome AF: 0.000658

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.00640

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00457

Gnomad4 FIN exome AF: 0.00700

Gnomad4 NFE exome AF: 0.00237

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.00259 AC: 395 AN: 152230 Hom.: 4 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74424

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00585

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00313 Hom.: 2

Bravo AF: 0.00226

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.00326 AC: 27

ExAC AF: 0.00383 AC: 463

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00616

EpiControl AF: 0.00522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.038	T;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.51	.;.;T
MetaRNN	Benign	0.0053	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.63	N;N;N
REVEL	Benign	0.080
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.13	T;T;T
MVP		0.16
MPC		0.10
ClinPred		0.020	T
GERP RS		2.0
Varity_R		0.10

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: rs28919926; hg19: chr5-42800866;