16-19536412-T-G

Variant names:

• chr16-19536412-T-G
• rs763871078
• NM_001323572.2:c.743T>G

Variant summary

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

The NM_001323572.2(CCP110):​c.743T>G​(p.Leu248Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

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=0.31782615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCP110	NM_001323572.2	c.743T>G	p.Leu248Arg	missense_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.743T>G	p.Leu248Arg	missense_variant	Exon 4 of 14		NM_001323572.2	ENSP00000511625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.38
MutPred		0.37		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.41
MPC		0.88
ClinPred		0.69	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs763871078; hg19: chr16-19547734;