rs2053729876

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014812.3(CEP170):c.4554A>T(p.Lys1518Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,408,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CEP170
NM_014812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.404

Publications

0 publications found

Variant links:

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]

CEP170 links:

ENSG00000227230 (HGNC:):

ENSG00000227230 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17262644).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3 link	c.4554A>T	p.Lys1518Asn	missense_variant	Exon 20 of 20	ENST00000366542.6	NP_055627.2	Q5SW79-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP170	ENST00000366542.6 link	c.4554A>T	p.Lys1518Asn	missense_variant	Exon 20 of 20	5	NM_014812.3	ENSP00000355500.1	Q5SW79-1
CEP170	ENST00000366544.6 link	c.4260A>T	p.Lys1420Asn	missense_variant	Exon 19 of 19	5		ENSP00000355502.1	Q5SW79-3
CEP170	ENST00000366543.5 link	c.4182A>T	p.Lys1394Asn	missense_variant	Exon 19 of 19	5		ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000135

AC:

AN:

1408940

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

695430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32196

American (AMR)

AF:

0.00

AC:

AN:

36668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25240

East Asian (EAS)

AF:

0.00

AC:

AN:

36966

South Asian (SAS)

AF:

0.00

AC:

AN:

80296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000175

AC:

AN:

1082872

Other (OTH)

AF:

0.00

AC:

AN:

58546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4554A>T (p.K1518N) alteration is located in exon 20 (coding exon 19) of the CEP170 gene. This alteration results from a A to T substitution at nucleotide position 4554, causing the lysine (K) at amino acid position 1518 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.;.;.;T

Eigen

Benign

-0.045

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.96

.;.;.;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.;.;.;.

PhyloP100

0.40

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Benign

0.30

T;T;T;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.23

MutPred

0.18

Loss of methylation at K1518 (P = 0.0028);.;.;.;.;

MVP

0.59

ClinPred

0.63

GERP RS

3.7

Varity_R

0.11

gMVP

0.31

Mutation Taster

=57/43

polymorphism

(source)

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

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rs2053729876

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over