5-42799708-G-T

Variant names:

• chr5-42799708-G-T
• NM_001134848.2:c.692G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001134848.2(CCDC152):​c.692G>T​(p.Arg231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,512 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC152 NM_001134848.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

Genes affected

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3418949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC152	NM_001134848.2	c.692G>T	p.Arg231Leu	missense_variant	Exon 9 of 9	ENST00000361970.10	NP_001128320.1
SELENOP	NM_005410.4	c.*1012C>A		downstream_gene_variant		ENST00000514985.6	NP_005401.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC152	ENST00000361970.10	c.692G>T	p.Arg231Leu	missense_variant	Exon 9 of 9	1	NM_001134848.2	ENSP00000354888.5
CCDC152	ENST00000388827.4	c.524G>T	p.Arg175Leu	missense_variant	Exon 7 of 7	2		ENSP00000373479.4
SELENOP	ENST00000514985.6	c.*1012C>A		downstream_gene_variant		1	NM_005410.4	ENSP00000420939.1
SELENOP	ENST00000512980.5	n.*175C>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398512 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.92	P;.
Vest4		0.48
MutPred		0.30		Loss of MoRF binding (P = 0.0102);.;
MVP		0.39
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-42799810;