1-86371029-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366781.1(ODF2L):ā€‹c.1045A>Gā€‹(p.Thr349Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,569,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

ODF2L
NM_001366781.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.298
Variant links:
Genes affected
ODF2L (HGNC:29225): (outer dense fiber of sperm tails 2 like) Involved in negative regulation of cilium assembly. Located in centriolar satellite and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052562803).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ODF2LNM_001366781.1 linkc.1045A>G p.Thr349Ala missense_variant 10/17 ENST00000460698.7 NP_001353710.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ODF2LENST00000460698.7 linkc.1045A>G p.Thr349Ala missense_variant 10/175 NM_001366781.1 ENSP00000433092.2 Q9ULJ1-4H0YD68

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
33
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:
0.0000313
AC:
7
AN:
223790
Hom.:
0
AF XY:
0.0000496
AC XY:
6
AN XY:
120940
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:
0.00
Gnomad NFE exome
AF:
0.0000659
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000289
AC:
41
AN:
1417114
Hom.:
0
Cov.:
25
AF XY:
0.0000298
AC XY:
21
AN XY:
704076
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:
0.0000302
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
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
Bravo
AF:
0.00000756
ExAC
AF:
0.0000330
AC:
4

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 GeneticsMay 28, 2024The c.1045A>G (p.T349A) alteration is located in exon 10 (coding exon 9) of the ODF2L gene. This alteration results from a A to G substitution at nucleotide position 1045, causing the threonine (T) at amino acid position 349 to be replaced by an alanine (A). 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
0.084
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
14
DANN
Benign
0.87
DEOGEN2
Benign
0.0099
T;T;.;.;T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.65
.;T;T;T;T;T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.053
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;.;L;L;L;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.97
N;N;N;N;N;N
REVEL
Benign
0.026
Sift
Benign
0.66
T;T;T;T;T;T
Sift4G
Benign
0.76
T;T;T;T;T;.
Polyphen
0.048
B;.;.;B;B;.
Vest4
0.066
MutPred
0.20
Loss of stability (P = 0.0241);.;Loss of stability (P = 0.0241);Loss of stability (P = 0.0241);Loss of stability (P = 0.0241);.;
MVP
0.46
MPC
0.011
ClinPred
0.027
T
GERP RS
1.7
Varity_R
0.022
gMVP
0.043

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: rs771224704; hg19: chr1-86836712; API