Variant chr6-167004287-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007045.4(CEP43):c.324G>T(p.Glu108Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,606,940 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

CEP43
NM_007045.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017407238).

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP43	NM_007045.4 linkuse as main transcript	c.324G>T	p.Glu108Asp	missense_variant	5/13	ENST00000366847.9
CEP43	NM_194429.3 linkuse as main transcript	c.324G>T	p.Glu108Asp	missense_variant	5/12
CEP43	NM_001278690.2 linkuse as main transcript	c.324G>T	p.Glu108Asp	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP43	ENST00000366847.9 linkuse as main transcript	c.324G>T	p.Glu108Asp	missense_variant	5/13	1	NM_007045.4	P4	O95684-1

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00114

AC:

281

AN:

246470

Hom.:

AF XY:

0.00138

AC XY:

184

AN XY:

133184

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000481

Gnomad ASJ exome

AF:

0.000405

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00202

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00110

AC:

1598

AN:

1454708

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

846

AN XY:

723582

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000715

Gnomad4 ASJ exome

AF:

0.000309

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00198

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000979

AC:

149

AN:

152232

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.000910

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00120

AC:

146

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 06, 2022

The c.324G>T (p.E108D) alteration is located in exon 5 (coding exon 5) of the FGFR1OP gene. This alteration results from a G to T substitution at nucleotide position 324, causing the glutamic acid (E) at amino acid position 108 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

L;.;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.42

N;.;N

REVEL

Benign

0.088

Sift

Benign

0.22

T;.;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.12

B;.;B

Vest4

0.38

MutPred

0.45

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.41

MPC

0.086

ClinPred

0.022

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.20

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.

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