5-42759197-C-A

Variant summary

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

The NM_001134848.2(CCDC152):c.76C>A(p.Gln26Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: 1.38

Genes affected

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

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=0.16038182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC152	NM_001134848.2	c.76C>A	p.Gln26Lys	missense_variant	2/9	ENST00000361970.10
CCDC152	XM_047416584.1	c.139C>A	p.Gln47Lys	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC152	ENST00000361970.10	c.76C>A	p.Gln26Lys	missense_variant	2/9	1	NM_001134848.2	P1
CCDC152	ENST00000388827.4	c.76C>A	p.Gln26Lys	missense_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 18, 2023

The c.76C>A (p.Q26K) alteration is located in exon 2 (coding exon 1) of the CCDC152 gene. This alteration results from a C to A substitution at nucleotide position 76, causing the glutamine (Q) at amino acid position 26 to be replaced by a lysine (K). 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	0.075
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	0.023
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.67	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.094
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.48	T;T
Polyphen		0.041	B;.
Vest4		0.27
MutPred		0.16		Loss of ubiquitination at K29 (P = 0.0248);Loss of ubiquitination at K29 (P = 0.0248);
MVP		0.067
ClinPred		0.91	D
GERP RS		4.2
Varity_R		0.24
gMVP		0.19

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: chr5-42759299;