6-167013534-G-C

Variant summary

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

The NM_007045.4(CEP43):c.546G>C(p.Lys182Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CEP43
NM_007045.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

CEP43 (HGNC:17012): (centrosomal protein 43) This gene encodes a largely hydrophilic centrosomal protein that is required for anchoring microtubules to subcellular structures. A t(6;8)(q27;p11) chromosomal translocation, fusing this gene and the fibroblast growth factor receptor 1 (FGFR1) gene, has been found in cases of myeloproliferative disorder. The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic domain of FGFR1. Alterations in this gene may also be associated with Crohn's disease, Graves' disease, and vitiligo. Alternatively spliced transcript variants that encode different proteins have been identified. [provided by RefSeq, Jul 2013]

CEP43 links:

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=0.09393683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP43	NM_007045.4 linkuse as main transcript	c.546G>C	p.Lys182Asn	missense_variant	7/13	ENST00000366847.9
CEP43	NM_001278690.2 linkuse as main transcript	c.439-8875G>C		intron_variant
CEP43	NM_194429.3 linkuse as main transcript	c.519+2641G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9 linkuse as main transcript	c.546G>C	p.Lys182Asn	missense_variant	7/13	1	NM_007045.4	P4	O95684-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251274

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000479

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.546G>C (p.K182N) alteration is located in exon 7 (coding exon 7) of the FGFR1OP gene. This alteration results from a G to C substitution at nucleotide position 546, causing the lysine (K) at amino acid position 182 to be replaced by an asparagine (N). 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

Benign

0.28

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.072

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.59

M_CAP

Benign

0.0034

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.61

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.090

REVEL

Benign

0.097

Sift

Benign

0.086

Sift4G

Benign

0.49

Polyphen

0.0020

Vest4

0.32

MutPred

0.23

Loss of methylation at K182 (P = 0.0157);

MVP

0.54

MPC

0.051

ClinPred

0.16

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.041

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over