dbSNP rs745381316: CEP350:p.Arg125Ser (chr1-179992199-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014810.5(CEP350):c.373C>A(p.Arg125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R125G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

CEP350
NM_014810.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.265498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP350	NM_014810.5 link	c.373C>A	p.Arg125Ser	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.373C>A	p.Arg125Ser	missense_variant	Exon 5 of 38	1	NM_014810.5	ENSP00000356579.3		Q5VT06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.43e-7

AC:

AN:

1345938

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27666

American (AMR)

AF:

0.00

AC:

AN:

20462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23290

East Asian (EAS)

AF:

0.00

AC:

AN:

32940

South Asian (SAS)

AF:

0.0000146

AC:

AN:

68666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062146

Other (OTH)

AF:

0.00

AC:

AN:

55568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.4

M;.;.

PhyloP100

2.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

N;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.58

MutPred

0.25

Loss of MoRF binding (P = 0.0139);.;.;

MVP

0.51

MPC

0.40

ClinPred

0.96

GERP RS

5.6

Varity_R

0.25

gMVP

0.28

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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