4-174308707-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040157.3(CEP44):​c.526C>T​(p.Arg176Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,604,792 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: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

CEP44
NM_001040157.3 missense

Scores

13
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52
Variant links:
Genes affected
CEP44 (HGNC:29356): (centrosomal protein 44) Enables microtubule binding activity. Involved in centriole replication and centriole-centriole cohesion. Located in centriole; centrosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09826565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP44NM_001040157.3 linkc.526C>T p.Arg176Cys missense_variant Exon 7 of 12 ENST00000503780.6 NP_001035247.1 Q9C0F1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP44ENST00000503780.6 linkc.526C>T p.Arg176Cys missense_variant Exon 7 of 12 1 NM_001040157.3 ENSP00000423153.1 Q9C0F1-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000161
AC:
40
AN:
248838
Hom.:
0
AF XY:
0.000178
AC XY:
24
AN XY:
134528
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000178
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000982
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000602
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000489
AC:
71
AN:
1452642
Hom.:
0
Cov.:
31
AF XY:
0.0000541
AC XY:
39
AN XY:
720970
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.000159
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000329
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000431
Gnomad4 NFE exome
AF:
0.0000208
Gnomad4 OTH exome
AF:
0.0000666
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000867
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.526C>T (p.R176C) alteration is located in exon 7 (coding exon 5) of the CEP44 gene. This alteration results from a C to T substitution at nucleotide position 526, causing the arginine (R) at amino acid position 176 to be replaced by a cysteine (C). 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
0.46
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;T;T;.
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.94
.;.;D;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.098
T;T;T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.1
M;M;.;M;M
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.9
D;D;D;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
1.0
D;D;.;D;D
Vest4
0.70
MVP
0.79
MPC
0.51
ClinPred
0.24
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148258730; hg19: chr4-175229858; COSMIC: COSV56659194; COSMIC: COSV56659194; API