Variant 22-50530743-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001014440.4(CIMAP1B):c.650A>C(p.Lys217Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,610,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

CIMAP1B
NM_001014440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

Variant links:

Genes affected

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10954687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1B	NM_001014440.4 link	c.650A>C	p.Lys217Thr	missense_variant	6/7	ENST00000329363.9	NP_001014440.2	A8MYP8-1A1L1A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF3B	ENST00000329363.9 link	c.650A>C	p.Lys217Thr	missense_variant	6/7	5	NM_001014440.4	ENSP00000382804.2		A8MYP8-1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000973

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:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000310

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

242360

Hom.:

AF XY:

0.000166

AC XY:

AN XY:

132424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000482

Gnomad NFE exome

AF:

0.000374

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000289

AC:

422

AN:

1459132

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

187

AN XY:

725734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000573

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000178

AC:

AN:

151386

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

73924

show subpopulations

Gnomad4 AFR

AF:

0.0000973

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000310

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000608

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Feb 27, 2024

The c.650A>C (p.K217T) alteration is located in exon 6 (coding exon 5) of the ODF3B gene. This alteration results from a A to C substitution at nucleotide position 650, causing the lysine (K) at amino acid position 217 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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;T

Sift4G

Benign

0.12

T;T

Polyphen

0.93

P;.

Vest4

0.25

MutPred

0.074

Loss of helix (P = 0.079);.;

MVP

0.18

ClinPred

0.18

GERP RS

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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