5-42800622-A-G

Variant names:

• chr5-42800622-A-G
• rs6413428
• NM_005410.4:c.*98T>C

Variant summary

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

The NM_005410.4(SELENOP):​c.*98T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,378,504 control chromosomes in the GnomAD database, including 41,137 homozygotes. 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 0.26 (5519 hom., cov: 33)
  • Exomes 𝑓: 0.23 (35618 hom.)
• Consequence: SELENOP NM_005410.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 20 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	NM_005410.4	MANE Select	c.*98T>C		3_prime_UTR	Exon 5 of 5	NP_005401.3
	CCDC152	NM_001134848.2	MANE Select	c.*841A>G		3_prime_UTR	Exon 9 of 9	NP_001128320.1
	SELENOP	NM_001093726.3		c.*98T>C		3_prime_UTR	Exon 6 of 6	NP_001087195.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.*98T>C		3_prime_UTR	Exon 5 of 5	ENSP00000420939.1
	CCDC152	ENST00000361970.10	TSL:1 MANE Select	c.*841A>G		3_prime_UTR	Exon 9 of 9	ENSP00000354888.5
	SELENOP	ENST00000506577.5	TSL:1	c.*98T>C		3_prime_UTR	Exon 5 of 5	ENSP00000425915.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39011 AN: 152042 Hom.: 5509 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.233 AC: 285556 AN: 1226344 Hom.: 35618 Cov.: 17 AF XY: 0.231 AC XY: 139350 AN XY: 604482

African (AFR) AF: 0.349 AC: 9728 AN: 27854

American (AMR) AF: 0.154 AC: 4208 AN: 27362

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 4970 AN: 19100

East Asian (EAS) AF: 0.000343 AC: 13 AN: 37904

South Asian (SAS) AF: 0.130 AC: 8107 AN: 62324

European-Finnish (FIN) AF: 0.288 AC: 12541 AN: 43568

Middle Eastern (MID) AF: 0.237 AC: 1095 AN: 4618

European-Non Finnish (NFE) AF: 0.245 AC: 232760 AN: 951952

Other (OTH) AF: 0.235 AC: 12134 AN: 51662

GnomAD4 genome AF: 0.257 AC: 39050 AN: 152160 Hom.: 5519 Cov.: 33 AF XY: 0.252 AC XY: 18780 AN XY: 74416

African (AFR) AF: 0.345 AC: 14315 AN: 41462

American (AMR) AF: 0.193 AC: 2952 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.123 AC: 592 AN: 4830

European-Finnish (FIN) AF: 0.285 AC: 3014 AN: 10592

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16324 AN: 68000

Other (OTH) AF: 0.261 AC: 550 AN: 2110

Alfa AF: 0.242 Hom.: 12557

Bravo AF: 0.256

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		0.70
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: rs6413428; hg19: chr5-42800724;