16-19536181-C-T

Variant names:

• chr16-19536181-C-T
• rs3751821
• NM_001323572.2:c.512C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323572.2(CCP110):​c.512C>T​(p.Pro171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,600 control chromosomes in the GnomAD database, including 13,971 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2930 hom., cov: 32)
  • Exomes 𝑓: 0.097 (11041 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.230
• Publications: 28 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002224356).
• BP6: Variant 16-19536181-C-T is Benign according to our data. Variant chr16-19536181-C-T is described in ClinVar as Benign. ClinVar VariationId is 402511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

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.512C>T	p.Pro171Leu	missense	Exon 4 of 14	NP_001310501.1	O43303-2
	CCP110	NM_001199022.3		c.512C>T	p.Pro171Leu	missense	Exon 4 of 15	NP_001185951.2	O43303-1
	CCP110	NM_001323569.2		c.512C>T	p.Pro171Leu	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.512C>T	p.Pro171Leu	missense	Exon 4 of 14	ENSP00000511625.1	O43303-2
	CCP110	ENST00000381396.9	TSL:1	c.512C>T	p.Pro171Leu	missense	Exon 4 of 15	ENSP00000370803.5	O43303-1
	CCP110	ENST00000396208.4	TSL:1	c.512C>T	p.Pro171Leu	missense	Exon 3 of 13	ENSP00000379511.2	O43303-2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24428 AN: 151916 Hom.: 2913 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.147 AC: 37037 AN: 251278 AF XY: 0.137

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.0556

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.0694

Gnomad NFE exome AF: 0.0695

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0967 AC: 141351 AN: 1461566 Hom.: 11041 Cov.: 32 AF XY: 0.0962 AC XY: 69975 AN XY: 727088

African (AFR) AF: 0.304 AC: 10163 AN: 33462

American (AMR) AF: 0.287 AC: 12840 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 1447 AN: 26126

East Asian (EAS) AF: 0.390 AC: 15490 AN: 39682

South Asian (SAS) AF: 0.129 AC: 11157 AN: 86248

European-Finnish (FIN) AF: 0.0690 AC: 3687 AN: 53408

Middle Eastern (MID) AF: 0.0981 AC: 566 AN: 5768

European-Non Finnish (NFE) AF: 0.0713 AC: 79252 AN: 1111764

Other (OTH) AF: 0.112 AC: 6749 AN: 60388

GnomAD4 genome AF: 0.161 AC: 24476 AN: 152034 Hom.: 2930 Cov.: 32 AF XY: 0.164 AC XY: 12199 AN XY: 74310

African (AFR) AF: 0.295 AC: 12221 AN: 41448

American (AMR) AF: 0.225 AC: 3433 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2028 AN: 5142

South Asian (SAS) AF: 0.137 AC: 659 AN: 4822

European-Finnish (FIN) AF: 0.0726 AC: 767 AN: 10562

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4791 AN: 67996

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.103 Hom.: 5582

Bravo AF: 0.180

TwinsUK AF: 0.0769 AC: 285

ALSPAC AF: 0.0778 AC: 300

ESP6500AA AF: 0.289 AC: 1269

ESP6500EA AF: 0.0657 AC: 565

ExAC AF: 0.142 AC: 17260

Asia WGS AF: 0.241 AC: 836 AN: 3478

EpiCase AF: 0.0745

EpiControl AF: 0.0745

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.37
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.71	N
PhyloP100		-0.23
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.18
ClinPred		0.00046	T
GERP RS		-2.3
Varity_R		0.019
gMVP		0.069
Mutation Taster		=100/0	polymorphism (auto)

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: rs3751821; hg19: chr16-19547503; COSMIC: COSV66816727;