22-50530959-C-G

Variant summary

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

The NM_001014440.4(ODF3B):ā€‹c.518G>Cā€‹(p.Ser173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,896 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ODF3B
NM_001014440.4 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.281
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]

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=0.072782755).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ODF3BNM_001014440.4 linkuse as main transcriptc.518G>C p.Ser173Thr missense_variant 5/7 ENST00000329363.9 NP_001014440.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CIMAP1BENST00000329363.9 linkuse as main transcriptc.518G>C p.Ser173Thr missense_variant 5/75 NM_001014440.4 ENSP00000382804 P4A8MYP8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458896
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725674
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJan 31, 2024The c.518G>C (p.S173T) alteration is located in exon 5 (coding exon 4) of the ODF3B gene. This alteration results from a G to C substitution at nucleotide position 518, causing the serine (S) at amino acid position 173 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
0.097
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.39
T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.073
T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
0.66
N;N;N;N;N
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.091
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.053
T;T
Polyphen
0.020
B;.
Vest4
0.29
MutPred
0.17
Gain of sheet (P = 0.0477);.;
MVP
0.16
ClinPred
0.15
T
GERP RS
3.7

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: rs957214745; hg19: chr22-50969388; API