Genetic Variant CEP350:p.Lys20Arg (chr1-179986240-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014810.5(CEP350):c.59A>G(p.Lys20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 1 hom. )

Consequence

CEP350
NM_014810.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

1 publications found

Variant links:

Genes affected

CEP350 (HGNC:24238): (centrosomal protein 350) The product of this gene is a large protein with a CAP-Gly domain typically found in cytoskeleton-associated proteins. The encoded protein primarily localizes to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. The encoded protein directly interacts with another large centrosomal protein and is required to anchor microtubules at the centrosome. It is also implicated in the regulation of a class of nuclear hormone receptors in the nucleus. Several alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

CEP350 links:

ENSG00000303101 (HGNC:):

ENSG00000303101 links:

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ACMG classification

Classification was made for transcript

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=0.09314138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP350	NM_014810.5 link	c.59A>G	p.Lys20Arg	missense_variant	Exon 2 of 38	ENST00000367607.8	NP_055625.4	Q5VT06

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP350	ENST00000367607.8 link	c.59A>G	p.Lys20Arg	missense_variant	Exon 2 of 38	1	NM_014810.5	ENSP00000356579.3		Q5VT06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000623

AC:

AN:

160472

AF XY:

0.0000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1398288

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31588

American (AMR)

AF:

0.00

AC:

AN:

35714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

35702

South Asian (SAS)

AF:

0.00

AC:

AN:

79084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5386

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1078426

Other (OTH)

AF:

0.00

AC:

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.59A>G (p.K20R) alteration is located in exon 2 (coding exon 1) of the CEP350 gene. This alteration results from a A to G substitution at nucleotide position 59, causing the lysine (K) at amino acid position 20 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

0.074

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

-0.080

Eigen_PC

Benign

0.070

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

L;.

PhyloP100

1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.031

Sift

Uncertain

0.020

D;T

Sift4G

Benign

0.39

T;T

Polyphen

0.36

B;.

Vest4

0.085

MVP

0.35

MPC

0.059

ClinPred

0.25

GERP RS

4.9

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.062

gMVP

0.067

Mutation Taster

=91/9

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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1-179986240-A-G

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