Variant 1-243140049-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_014812.3(CEP170):c.4118A>G(p.His1373Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CEP170
NM_014812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, CEP170

BP4

Computational evidence support a benign effect (MetaRNN=0.1796433).

BS2

High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170	NM_014812.3 linkuse as main transcript	c.4118A>G	p.His1373Arg	missense_variant	16/20	ENST00000366542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170	ENST00000366542.6 linkuse as main transcript	c.4118A>G	p.His1373Arg	missense_variant	16/20	5	NM_014812.3	P1	Q5SW79-1
	ENST00000439562.1 linkuse as main transcript	n.155T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249212

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000828

AC:

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

May 05, 2023

The c.4118A>G (p.H1373R) alteration is located in exon 16 (coding exon 15) of the CEP170 gene. This alteration results from a A to G substitution at nucleotide position 4118, causing the histidine (H) at amino acid position 1373 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.043

T;.;.;.;T;.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

2.0

M;.;.;.;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;D

REVEL

Benign

0.061

Sift

Benign

0.030

D;T;T;T;T;T;T;D

Sift4G

Benign

0.20

T;T;T;T;T;T;.;.

Polyphen

0.049

B;P;P;.;.;.;.;.

Vest4

0.47

MutPred

0.20

Gain of MoRF binding (P = 0.0206);.;.;.;.;.;.;.;

MVP

0.35

ClinPred

0.24

GERP RS

5.3

Varity_R

0.17

gMVP

0.16

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