16-19536794-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001323572.2(CCP110):c.1125G>A(p.Met375Ile) variant causes a missense change. The variant allele was found at a frequency of 0.15 in 1,613,874 control chromosomes in the GnomAD database, including 18,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16986 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.39

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015616417).
• BP6: Variant 16-19536794-G-A is Benign according to our data. Variant chr16-19536794-G-A is described in ClinVar as [Benign]. Clinvar id is 402513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCP110	NM_001323572.2	c.1125G>A	p.Met375Ile	missense_variant	4/14	ENST00000694978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCP110	ENST00000694978.1	c.1125G>A	p.Met375Ile	missense_variant	4/14		NM_001323572.2	P4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23341 AN: 152064 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.148 AC: 37144 AN: 250300 Hom.: 2901 AF XY: 0.144 AC XY: 19518 AN XY: 135484

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.155

Gnomad SAS exome AF: 0.0861

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.150 AC: 218810 AN: 1461694 Hom.: 16986 Cov.: 37 AF XY: 0.148 AC XY: 107581 AN XY: 727130

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.0853

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.153 AC: 23344 AN: 152180 Hom.: 1858 Cov.: 32 AF XY: 0.153 AC XY: 11384 AN XY: 74408

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.169

Alfa AF: 0.150 Hom.: 4371

Bravo AF: 0.163

TwinsUK AF: 0.150 AC: 557

ALSPAC AF: 0.145 AC: 558

ESP6500AA AF: 0.158 AC: 696

ESP6500EA AF: 0.156 AC: 1341

ExAC AF: 0.145 AC: 17594

Asia WGS AF: 0.126 AC: 440 AN: 3478

EpiCase AF: 0.153

EpiControl AF: 0.156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
Cadd	Uncertain	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M
MutationTaster	Benign	0.0026	P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.26
MutPred		0.24		Gain of methylation at K374 (P = 0.0244);Gain of methylation at K374 (P = 0.0244);Gain of methylation at K374 (P = 0.0244);
MPC		0.68
ClinPred		0.022	T
GERP RS		4.0
Varity_R		0.76
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: rs7190666; hg19: chr16-19548116; COSMIC: COSV66816649; COSMIC: COSV66816649;