chr1-179990604-G-T

Variant summary

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

The NM_014810.5(CEP350):​c.218G>T​(p.Arg73Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R73Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CEP350
NM_014810.5 missense

Scores

3
12
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.09

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]

Genome browser will be placed here

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
CEP350NM_014810.5 linkc.218G>T p.Arg73Leu missense_variant Exon 4 of 38 ENST00000367607.8 NP_055625.4 Q5VT06

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP350ENST00000367607.8 linkc.218G>T p.Arg73Leu missense_variant Exon 4 of 38 1 NM_014810.5 ENSP00000356579.3 Q5VT06

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1431862
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
711360
African (AFR)
AF:
0.00
AC:
0
AN:
32832
American (AMR)
AF:
0.00
AC:
0
AN:
42680
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25592
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39084
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5708
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1092020
Other (OTH)
AF:
0.00
AC:
0
AN:
59298
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Uncertain
2.4
M;.
PhyloP100
7.1
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.4
N;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.73
MutPred
0.43
Gain of sheet (P = 0.0043);.;
MVP
0.47
MPC
0.45
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.30
gMVP
0.22
Mutation Taster
=50/50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs780482124; hg19: chr1-179959739; API