16-19536521-CTG-C

Variant names:

• chr16-19536521-CTG-C
• NM_001323572.2:c.856_857delGT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001323572.2(CCP110):​c.856_857delGT​(p.Val286LeufsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCP110 NM_001323572.2 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.37

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-19536521-CTG-C is Pathogenic according to our data. Variant chr16-19536521-CTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2681727.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCP110	NM_001323572.2	c.856_857delGT	p.Val286LeufsTer5	frameshift_variant	Exon 4 of 14	ENST00000694978.1	NP_001310501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCP110	ENST00000694978.1	c.856_857delGT	p.Val286LeufsTer5	frameshift_variant	Exon 4 of 14		NM_001323572.2	ENSP00000511625.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

See cases Pathogenic:1

Dec 25, 2023

Center for Medical Genetics, Keio University School of Medicine

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

No functional analysis has been performed on this variant, but it is a frameshift and a predicted loss of function. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19547843;