16-19536603-A-G

Variant names:

• chr16-19536603-A-G
• rs761555016
• NM_001323572.2:c.934A>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.934A>G​(p.Met312Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,070 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. M312L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• 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=0.018721998).

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.934A>G	p.Met312Val	missense	Exon 4 of 14	NP_001310501.1	O43303-2
	CCP110	NM_001199022.3		c.934A>G	p.Met312Val	missense	Exon 4 of 15	NP_001185951.2	O43303-1
	CCP110	NM_001323569.2		c.934A>G	p.Met312Val	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.934A>G	p.Met312Val	missense	Exon 4 of 14	ENSP00000511625.1	O43303-2
	CCP110	ENST00000381396.9	TSL:1	c.934A>G	p.Met312Val	missense	Exon 4 of 15	ENSP00000370803.5	O43303-1
	CCP110	ENST00000396208.4	TSL:1	c.934A>G	p.Met312Val	missense	Exon 3 of 13	ENSP00000379511.2	O43303-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251104 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727216

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: 0.00 AC: 0 AN: 39696

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

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.53
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.0020
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.052
Sift	Benign	0.80	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.14		Loss of disorder (P = 0.1058)
MVP		0.092
MPC		0.18
ClinPred		0.028	T
GERP RS		-7.6
Varity_R		0.025
gMVP		0.049
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs761555016; hg19: chr16-19547925;