16-19537418-A-T

Variant names:

• chr16-19537418-A-T
• rs17227190
• NM_001323572.2:c.1749A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001323572.2(CCP110):​c.1749A>T​(p.Lys583Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K583K) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: CCP110 NM_001323572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 11 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03350386).

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.1749A>T	p.Lys583Asn	missense	Exon 4 of 14	NP_001310501.1	O43303-2
	CCP110	NM_001199022.3		c.1749A>T	p.Lys583Asn	missense	Exon 4 of 15	NP_001185951.2	O43303-1
	CCP110	NM_001323569.2		c.1749A>T	p.Lys583Asn	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.1749A>T	p.Lys583Asn	missense	Exon 4 of 14	ENSP00000511625.1	O43303-2
	CCP110	ENST00000381396.9	TSL:1	c.1749A>T	p.Lys583Asn	missense	Exon 4 of 15	ENSP00000370803.5	O43303-1
	CCP110	ENST00000396208.4	TSL:1	c.1749A>T	p.Lys583Asn	missense	Exon 3 of 13	ENSP00000379511.2	O43303-2

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000219 AC: 55 AN: 250780 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1461300 Hom.: 0 Cov.: 32 AF XY: 0.0000729 AC XY: 53 AN XY: 726938

African (AFR) AF: 0.0000299 AC: 1 AN: 33426

American (AMR) AF: 0.00132 AC: 59 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111778

Other (OTH) AF: 0.000149 AC: 9 AN: 60374

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.000336 AC XY: 25 AN XY: 74498

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.00255 AC: 39 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 175

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.093
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.23
MutPred		0.36		Loss of ubiquitination at K583 (P = 0.0183)
MVP		0.50
MPC		0.41
ClinPred		0.11	T
GERP RS		4.4
Varity_R		0.21
gMVP		0.31
Mutation Taster		=72/28	polymorphism

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: rs17227190; hg19: chr16-19548740;