5-42799764-A-G

Variant names:

• chr5-42799764-A-G
• NM_001134848.2:c.748A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134848.2(CCDC152):​c.748A>G​(p.Lys250Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC152 NM_001134848.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17801887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC152	NM_001134848.2	c.748A>G	p.Lys250Glu	missense_variant	Exon 9 of 9	ENST00000361970.10	NP_001128320.1
SELENOP	NM_005410.4	c.*956T>C		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.748A>G	p.Lys250Glu	missense_variant	Exon 9 of 9	1	NM_001134848.2	ENSP00000354888.5
CCDC152	ENST00000388827.4	c.580A>G	p.Lys194Glu	missense_variant	Exon 7 of 7	2		ENSP00000373479.4
SELENOP	ENST00000514985.6	c.*956T>C		downstream_gene_variant		1	NM_005410.4	ENSP00000420939.1
SELENOP	ENST00000512980.5	n.*119T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.748A>G (p.K250E) alteration is located in exon 9 (coding exon 8) of the CCDC152 gene. This alteration results from a A to G substitution at nucleotide position 748, causing the lysine (K) at amino acid position 250 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.098
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.14
Sift	Benign	0.047	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.76	P;.
Vest4		0.32
MutPred		0.15		Loss of MoRF binding (P = 0.0102);.;
MVP		0.072
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-42799866;