16-19536642-A-C

Variant names:

• chr16-19536642-A-C
• rs760137709
• NM_001323572.2:c.973A>C

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.973A>C​(p.Ile325Leu) 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 1,461,850 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.282
• 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=0.037713975).

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.973A>C	p.Ile325Leu	missense	Exon 4 of 14	NP_001310501.1	O43303-2
	CCP110	NM_001199022.3		c.973A>C	p.Ile325Leu	missense	Exon 4 of 15	NP_001185951.2	O43303-1
	CCP110	NM_001323569.2		c.973A>C	p.Ile325Leu	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.973A>C	p.Ile325Leu	missense	Exon 4 of 14	ENSP00000511625.1	O43303-2
	CCP110	ENST00000381396.9	TSL:1	c.973A>C	p.Ile325Leu	missense	Exon 4 of 15	ENSP00000370803.5	O43303-1
	CCP110	ENST00000396208.4	TSL:1	c.973A>C	p.Ile325Leu	missense	Exon 3 of 13	ENSP00000379511.2	O43303-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461850 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.52
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.89	L
PhyloP100		0.28
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.025
Sift	Benign	0.53	T
Sift4G	Benign	0.62	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.27		Loss of methylation at K322 (P = 0.0545)
MVP		0.085
MPC		0.17
ClinPred		0.017	T
GERP RS		-7.9
Varity_R		0.028
gMVP		0.043

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: rs760137709; hg19: chr16-19547964;