NM_001323572.2:c.366A>G

Variant names:

• chr16-19536035-A-G
• rs10492785
• NM_001323572.2:c.366A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001323572.2(CCP110):​c.366A>G​(p.Thr122Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,613,528 control chromosomes in the GnomAD database, including 12,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2115 hom., cov: 32)
  • Exomes 𝑓: 0.094 (10243 hom.)
• Consequence: CCP110 NM_001323572.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.267
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-19536035-A-G is Benign according to our data. Variant chr16-19536035-A-G is described in ClinVar as Benign. ClinVar VariationId is 402510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.267 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCP110	NM_001323572.2	MANE Select	c.366A>G	p.Thr122Thr	synonymous	Exon 4 of 14	NP_001310501.1
	CCP110	NM_001199022.3		c.366A>G	p.Thr122Thr	synonymous	Exon 4 of 15	NP_001185951.2
	CCP110	NM_001323569.2		c.366A>G	p.Thr122Thr	synonymous	Exon 5 of 16	NP_001310498.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCP110	ENST00000694978.1	MANE Select	c.366A>G	p.Thr122Thr	synonymous	Exon 4 of 14	ENSP00000511625.1
	CCP110	ENST00000381396.9	TSL:1	c.366A>G	p.Thr122Thr	synonymous	Exon 4 of 15	ENSP00000370803.5
	CCP110	ENST00000396208.4	TSL:1	c.366A>G	p.Thr122Thr	synonymous	Exon 3 of 13	ENSP00000379511.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21207 AN: 152028 Hom.: 2102 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.141 AC: 35411 AN: 251184 AF XY: 0.132

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.0442

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.0693

Gnomad NFE exome AF: 0.0690

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0942 AC: 137634 AN: 1461382 Hom.: 10243 Cov.: 32 AF XY: 0.0940 AC XY: 68331 AN XY: 727010

African (AFR) AF: 0.229 AC: 7653 AN: 33462

American (AMR) AF: 0.283 AC: 12631 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 1114 AN: 26130

East Asian (EAS) AF: 0.390 AC: 15486 AN: 39670

South Asian (SAS) AF: 0.129 AC: 11128 AN: 86226

European-Finnish (FIN) AF: 0.0690 AC: 3684 AN: 53402

Middle Eastern (MID) AF: 0.0921 AC: 531 AN: 5766

European-Non Finnish (NFE) AF: 0.0711 AC: 79003 AN: 1111654

Other (OTH) AF: 0.106 AC: 6404 AN: 60374

GnomAD4 genome AF: 0.140 AC: 21251 AN: 152146 Hom.: 2115 Cov.: 32 AF XY: 0.143 AC XY: 10673 AN XY: 74388

African (AFR) AF: 0.223 AC: 9242 AN: 41470

American (AMR) AF: 0.215 AC: 3284 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2032 AN: 5162

South Asian (SAS) AF: 0.136 AC: 656 AN: 4826

European-Finnish (FIN) AF: 0.0722 AC: 767 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4759 AN: 68004

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.102 Hom.: 3272

Bravo AF: 0.155

Asia WGS AF: 0.237 AC: 821 AN: 3478

EpiCase AF: 0.0739

EpiControl AF: 0.0741

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		-0.27
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: rs10492785; hg19: chr16-19547357; COSMIC: COSV66816726;