Variant 1-243126601-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014812.3(CEP170):c.4603A>G(p.Thr1535Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,423,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000042 ( 0 hom. )

Consequence

CEP170
NM_014812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045288324).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP170	NM_014812.3 linkuse as main transcript	c.4603A>G	p.Thr1535Ala	missense_variant	20/20	ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6 linkuse as main transcript	c.4603A>G	p.Thr1535Ala	missense_variant	20/20	5	NM_014812.3	ENSP00000355500	P1	Q5SW79-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

177700

Hom.:

AF XY:

0.0000106

AC XY:

AN XY:

94568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000422

AC:

AN:

1423006

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

704014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.4603A>G (p.T1535A) alteration is located in exon 20 (coding exon 19) of the CEP170 gene. This alteration results from a A to G substitution at nucleotide position 4603, causing the threonine (T) at amino acid position 1535 to be replaced by an alanine (A). 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

Benign

0.057

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0061

T;.;.;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.65

.;.;.;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.045

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.44

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.27

T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.067

MutPred

0.062

Loss of glycosylation at T1535 (P = 0.0085);.;.;.;.;

MVP

0.29

ClinPred

0.028

GERP RS

-0.37

Varity_R

0.014

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over