16-19536850-T-A

Variant summary

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

The NM_001323572.2(CCP110):c.1181T>A(p.Ile394Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

Genes affected

CCP110 (HGNC:24342): (centriolar coiled-coil protein 110) Involved in centriole replication; negative regulation of cilium assembly; and regulation of cytokinesis. Located in centriole and centrosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3385048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCP110	NM_001323572.2	c.1181T>A	p.Ile394Lys	missense_variant	4/14	ENST00000694978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCP110	ENST00000694978.1	c.1181T>A	p.Ile394Lys	missense_variant	4/14		NM_001323572.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

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

Feb 06, 2024

The c.1181T>A (p.I394K) alteration is located in exon 4 (coding exon 3) of the CCP110 gene. This alteration results from a T to A substitution at nucleotide position 1181, causing the isoleucine (I) at amino acid position 394 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	24
Dann	Benign	0.96
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.87	P;P;P
Vest4		0.28
MutPred		0.38		Gain of solvent accessibility (P = 0.0038);Gain of solvent accessibility (P = 0.0038);Gain of solvent accessibility (P = 0.0038);
MVP		0.45
MPC		0.38
ClinPred		0.85	D
GERP RS		6.0
Varity_R		0.25
gMVP		0.45

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: chr16-19548172;