Genetic Variant CEP350:p.Thr111Ala (chr1-179992157-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014810.5(CEP350):c.331A>G(p.Thr111Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEP350
NM_014810.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP350	NM_014810.5 link	c.331A>G	p.Thr111Ala	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.331A>G	p.Thr111Ala	missense_variant	Exon 5 of 38	1	NM_014810.5	ENSP00000356579.3		Q5VT06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

156038

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384736

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29990

American (AMR)

AF:

0.00

AC:

AN:

28814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24558

East Asian (EAS)

AF:

0.00

AC:

AN:

35716

South Asian (SAS)

AF:

0.00

AC:

AN:

74206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1077884

Other (OTH)

AF:

0.00

AC:

AN:

57376

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.331A>G (p.T111A) alteration is located in exon 5 (coding exon 4) of the CEP350 gene. This alteration results from a A to G substitution at nucleotide position 331, causing the threonine (T) at amino acid position 111 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

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.4

M;.;.

PhyloP100

7.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.7

N;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.68

MutPred

0.19

Loss of sheet (P = 0.0104);.;.;

MVP

0.64

MPC

0.41

ClinPred

0.98

GERP RS

5.6

Varity_R

0.36

gMVP

0.25

Mutation Taster

=65/35

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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1-179992157-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