chr1-243139983-G-A

Variant names:

• chr1-243139983-G-A
• rs201404435
• NM_014812.3:c.4184C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014812.3(CEP170):​c.4184C>T​(p.Pro1395Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1395H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP170 NM_014812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 3 publications found

Genes affected

CEP170 (HGNC:28920): (centrosomal protein 170) The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000227230 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09591299).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014812.3. 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
	CEP170	NM_014812.3	MANE Select	c.4184C>T	p.Pro1395Leu	missense	Exon 16 of 20	NP_055627.2	Q5SW79-1
	CEP170	NM_001042404.2		c.3890C>T	p.Pro1297Leu	missense	Exon 15 of 19	NP_001035863.1	Q5SW79-3
	CEP170	NM_001042405.2		c.3812C>T	p.Pro1271Leu	missense	Exon 15 of 19	NP_001035864.1	Q5SW79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP170	ENST00000366542.6	TSL:5 MANE Select	c.4184C>T	p.Pro1395Leu	missense	Exon 16 of 20	ENSP00000355500.1	Q5SW79-1
	CEP170	ENST00000366544.6	TSL:5	c.3890C>T	p.Pro1297Leu	missense	Exon 15 of 19	ENSP00000355502.1	Q5SW79-3
	CEP170	ENST00000366543.5	TSL:5	c.3812C>T	p.Pro1271Leu	missense	Exon 15 of 19	ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247534 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461312 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726928

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111592

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.070
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Polyphen		0.14	B
Vest4		0.27
MutPred		0.23		Loss of catalytic residue at P1394 (P = 0.0107)
MVP		0.36
ClinPred		0.17	T
GERP RS		4.3
Varity_R		0.052
gMVP		0.13
Mutation Taster		=67/33	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: rs201404435; hg19: chr1-243303285;