16-19532441-T-C

Variant names:

• chr16-19532441-T-C
• NM_001323572.2:c.167T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001323572.2(CCP110):​c.167T>C​(p.Met56Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.34

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32783964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCP110	NM_001323572.2	c.167T>C	p.Met56Thr	missense_variant	Exon 3 of 14	ENST00000694978.1	NP_001310501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCP110	ENST00000694978.1	c.167T>C	p.Met56Thr	missense_variant	Exon 3 of 14		NM_001323572.2	ENSP00000511625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449966 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167T>C (p.M56T) alteration is located in exon 3 (coding exon 2) of the CCP110 gene. This alteration results from a T to C substitution at nucleotide position 167, causing the methionine (M) at amino acid position 56 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.63	P;P;P
Vest4		0.55
MutPred		0.26		Gain of phosphorylation at M56 (P = 0.0148);Gain of phosphorylation at M56 (P = 0.0148);Gain of phosphorylation at M56 (P = 0.0148);
MVP		0.44
MPC		0.23
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.47
gMVP		0.61

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: chr16-19543763;