16-19536181-C-G

Variant names:

• chr16-19536181-C-G
• rs3751821
• NM_001323572.2:c.512C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001323572.2(CCP110):​c.512C>G​(p.Pro171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P171L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 0 publications found

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]

CCP110 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056456506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323572.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCP110	NM_001323572.2	MANE Select	c.512C>G	p.Pro171Arg	missense	Exon 4 of 14	NP_001310501.1	O43303-2
	CCP110	NM_001199022.3		c.512C>G	p.Pro171Arg	missense	Exon 4 of 15	NP_001185951.2	O43303-1
	CCP110	NM_001323569.2		c.512C>G	p.Pro171Arg	missense	Exon 5 of 16	NP_001310498.1	O43303-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCP110	ENST00000694978.1	MANE Select	c.512C>G	p.Pro171Arg	missense	Exon 4 of 14	ENSP00000511625.1	O43303-2
	CCP110	ENST00000381396.9	TSL:1	c.512C>G	p.Pro171Arg	missense	Exon 4 of 15	ENSP00000370803.5	O43303-1
	CCP110	ENST00000396208.4	TSL:1	c.512C>G	p.Pro171Arg	missense	Exon 3 of 13	ENSP00000379511.2	O43303-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461780 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.9
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.23
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.039
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.18	B
Vest4		0.14
MutPred		0.14		Gain of catalytic residue at P171 (P = 0.0495)
MVP		0.12
MPC		0.22
ClinPred		0.16	T
GERP RS		-2.3
Varity_R		0.042
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3751821; hg19: chr16-19547503;