Variant chr22-50530509-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001014440.4(ODF3B):c.733G>A(p.Ala245Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,600,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ODF3B
NM_001014440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

ODF3B (HGNC:):

ODF3B links:

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27755624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3B	NM_001014440.4 linkuse as main transcript	c.733G>A	p.Ala245Thr	missense_variant	7/7	ENST00000329363.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1B	ENST00000329363.9 linkuse as main transcript	c.733G>A	p.Ala245Thr	missense_variant	7/7	5	NM_001014440.4	P4	A8MYP8-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000628

AC:

AN:

223066

Hom.:

AF XY:

0.0000658

AC XY:

AN XY:

121500

show subpopulations

Gnomad AFR exome

AF:

0.0000763

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000610

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

174

AN:

1448530

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

719482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

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:

0.000151

Gnomad4 OTH exome

AF:

0.0000836

GnomAD4 genome

AF:

0.000125

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000502

AC:

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 18, 2023

The c.733G>A (p.A245T) alteration is located in exon 7 (coding exon 6) of the ODF3B gene. This alteration results from a G to A substitution at nucleotide position 733, causing the alanine (A) at amino acid position 245 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0017

T;.;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.66

T;T;.

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.96

L;.;L

MutationTaster

Benign

0.73

D;D;D;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.74

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.87

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.25

B;.;B

Vest4

0.48

MutPred

0.41

Gain of phosphorylation at A245 (P = 0.0809);.;Gain of phosphorylation at A245 (P = 0.0809);

MVP

0.38

MPC

0.70

ClinPred

0.10

GERP RS

4.6

Varity_R

0.11

gMVP

0.35

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