chr16-19536365-G-A

Position:

• chr16-19536365-G-A

Variant summary

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

The NM_001323572.2(CCP110):​c.696G>A​(p.Met232Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14953291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCP110	NM_001323572.2	c.696G>A	p.Met232Ile	missense_variant	4/14	ENST00000694978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCP110	ENST00000694978.1	c.696G>A	p.Met232Ile	missense_variant	4/14		NM_001323572.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 16, 2023

The c.696G>A (p.M232I) alteration is located in exon 4 (coding exon 3) of the CCP110 gene. This alteration results from a G to A substitution at nucleotide position 696, causing the methionine (M) at amino acid position 232 to be replaced by an isoleucine (I). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;T;.
Eigen	Benign	0.061
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	0.70	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.082	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.049	B;B;B
Vest4		0.17
MutPred		0.35		Gain of methylation at K233 (P = 0.0225);Gain of methylation at K233 (P = 0.0225);Gain of methylation at K233 (P = 0.0225);
MVP		0.26
MPC		0.68
ClinPred		0.79	D
GERP RS		4.9
Varity_R		0.087
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs1970056740; hg19: chr16-19547687;