Genetic Variant CEP350:p.Val116Met (chr1-179992172-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014810.5(CEP350):c.346G>A(p.Val116Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000264 in 1,517,028 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: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CEP350
NM_014810.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10130769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP350	NM_014810.5 link	c.346G>A	p.Val116Met	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.346G>A	p.Val116Met	missense_variant	Exon 5 of 38	1	NM_014810.5	ENSP00000356579.3		Q5VT06

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000226

AC:

AN:

132526

AF XY:

0.0000141

show subpopulations

Gnomad AFR exome

AF:

0.000345

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:

0.0000176

AC:

AN:

1365240

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

674382

show subpopulations

African (AFR)

AF:

0.0000350

AC:

AN:

28558

American (AMR)

AF:

0.00

AC:

AN:

23612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23892

East Asian (EAS)

AF:

0.00

AC:

AN:

34430

South Asian (SAS)

AF:

0.00

AC:

AN:

71356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.0000205

AC:

AN:

1071010

Other (OTH)

AF:

0.0000177

AC:

AN:

56510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

151788

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67936

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000334

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.346G>A (p.V116M) alteration is located in exon 5 (coding exon 4) of the CEP350 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the valine (V) at amino acid position 116 to be replaced by a methionine (M). 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

0.38

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0043

T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.3

M;.;.

PhyloP100

4.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.78

N;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.50

MutPred

0.25

Gain of catalytic residue at V116 (P = 0.0021);.;.;

MVP

0.61

MPC

0.37

ClinPred

0.28

GERP RS

5.6

Varity_R

0.17

gMVP

0.20

Mutation Taster

=78/22

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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1-179992172-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over