5-42799764-A-G

Position:

• chr5-42799764-A-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)

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/exons	MANE	Protein	UniProt
CCDC152	NM_001134848.2	c.748A>G	p.Lys250Glu	missense_variant	9/9	ENST00000361970.10	NP_001128320.1
CCDC152	XM_047416584.1	c.811A>G	p.Lys271Glu	missense_variant	9/9		XP_047272540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC152	ENST00000361970.10	c.748A>G	p.Lys250Glu	missense_variant	9/9	1	NM_001134848.2	ENSP00000354888	P1
CCDC152	ENST00000388827.4	c.580A>G	p.Lys194Glu	missense_variant	7/7	2		ENSP00000373479

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

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;.
MutationTaster	Benign	1.0	N;N
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;