Genetic Variant CEP350:p.Pro91Ser (chr1-179992097-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014810.5(CEP350):c.271C>T(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P91A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CEP350
NM_014810.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057421327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP350	NM_014810.5 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 5 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.271C>T	p.Pro91Ser	missense_variant	Exon 5 of 38	1	NM_014810.5	ENSP00000356579.3		Q5VT06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000563

AC:

AN:

177556

AF XY:

0.0000105

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:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402662

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30828

American (AMR)

AF:

0.00

AC:

AN:

34552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25080

East Asian (EAS)

AF:

0.00

AC:

AN:

36300

South Asian (SAS)

AF:

0.00

AC:

AN:

76798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084508

Other (OTH)

AF:

0.00

AC:

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0036

T;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

PhyloP100

1.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;D;D

REVEL

Benign

0.025

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.17

T;D;D

Polyphen

0.0

B;B;.

Vest4

0.065

MutPred

0.31

Gain of sheet (P = 0.0061);.;.;

MVP

0.23

MPC

0.069

ClinPred

0.19

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.061

Mutation Taster

=93/7

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over