chr19-464062-G-A

Variant summary

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

The NM_182577.3(ODF3L2):​c.652C>T​(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,580,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ODF3L2
NM_182577.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55
Variant links:
Genes affected
CIMAP1D (HGNC:26841): (CIMAP1 family member D) Located in cytoplasmic microtubule. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41990092).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ODF3L2NM_182577.3 linkuse as main transcriptc.652C>T p.Arg218Cys missense_variant 4/4 ENST00000315489.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIMAP1DENST00000315489.5 linkuse as main transcriptc.652C>T p.Arg218Cys missense_variant 4/41 NM_182577.3 P2Q3SX64-1
CIMAP1DENST00000382696.7 linkuse as main transcriptc.544C>T p.Arg182Cys missense_variant 3/31 A2Q3SX64-2

Frequencies

GnomAD3 genomes
AF:
0.0000594
AC:
9
AN:
151632
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000585
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000859
AC:
16
AN:
186280
Hom.:
0
AF XY:
0.0000985
AC XY:
10
AN XY:
101524
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000361
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000500
Gnomad SAS exome
AF:
0.0000770
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000638
Gnomad OTH exome
AF:
0.000204
GnomAD4 exome
AF:
0.0000441
AC:
63
AN:
1428722
Hom.:
0
Cov.:
40
AF XY:
0.0000494
AC XY:
35
AN XY:
708134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000608
Gnomad4 AMR exome
AF:
0.0000254
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000419
Gnomad4 SAS exome
AF:
0.0000725
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000301
Gnomad4 OTH exome
AF:
0.0000845
GnomAD4 genome
AF:
0.0000593
AC:
9
AN:
151750
Hom.:
0
Cov.:
31
AF XY:
0.0000674
AC XY:
5
AN XY:
74166
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000586
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000844
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000518
AC:
6
Asia WGS
AF:
0.000577
AC:
2
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 submitterclinical testingAmbry GeneticsMay 17, 2023The c.652C>T (p.R218C) alteration is located in exon 4 (coding exon 4) of the ODF3L2 gene. This alteration results from a C to T substitution at nucleotide position 652, causing the arginine (R) at amino acid position 218 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.080
.;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.43
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.8
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.9
D;D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.50
MVP
0.46
MPC
1.0
ClinPred
0.86
D
GERP RS
3.8
Varity_R
0.61
gMVP
0.58

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: rs201870668; hg19: chr19-464062; COSMIC: COSV99199275; COSMIC: COSV99199275; API