NM_018319.4:c.429C>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_018319.4(TDP1):c.429C>T(p.Asp143Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,455,998 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 Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
TDP1
NM_018319.4 synonymous
NM_018319.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.94
Publications
0 publications found
Genes affected
TDP1 (HGNC:18884): (tyrosyl-DNA phosphodiesterase 1) The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). [provided by RefSeq, Aug 2016]
TDP1 Gene-Disease associations (from GenCC):
- spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- male infertility with azoospermia or oligozoospermia due to single gene mutationInheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 14-89963543-C-T is Benign according to our data. Variant chr14-89963543-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 586809.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.94 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018319.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TDP1 | NM_018319.4 | MANE Select | c.429C>T | p.Asp143Asp | synonymous | Exon 3 of 17 | NP_060789.2 | ||
| TDP1 | NM_001008744.2 | c.429C>T | p.Asp143Asp | synonymous | Exon 2 of 16 | NP_001008744.1 | |||
| TDP1 | NM_001330205.2 | c.429C>T | p.Asp143Asp | synonymous | Exon 2 of 15 | NP_001317134.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TDP1 | ENST00000335725.9 | TSL:1 MANE Select | c.429C>T | p.Asp143Asp | synonymous | Exon 3 of 17 | ENSP00000337353.4 | ||
| TDP1 | ENST00000393454.6 | TSL:1 | c.429C>T | p.Asp143Asp | synonymous | Exon 2 of 16 | ENSP00000377099.2 | ||
| TDP1 | ENST00000393452.7 | TSL:1 | c.429C>T | p.Asp143Asp | synonymous | Exon 3 of 18 | ENSP00000377098.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000121 AC: 3AN: 247320 AF XY: 0.0000150 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
247320
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1455998Hom.: 0 Cov.: 34 AF XY: 0.00000691 AC XY: 5AN XY: 723752 show subpopulations
GnomAD4 exome
AF:
AC:
8
AN:
1455998
Hom.:
Cov.:
34
AF XY:
AC XY:
5
AN XY:
723752
show subpopulations
African (AFR)
AF:
AC:
4
AN:
33164
American (AMR)
AF:
AC:
0
AN:
44018
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25750
East Asian (EAS)
AF:
AC:
1
AN:
39620
South Asian (SAS)
AF:
AC:
0
AN:
85558
European-Finnish (FIN)
AF:
AC:
0
AN:
53246
Middle Eastern (MID)
AF:
AC:
0
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1108834
Other (OTH)
AF:
AC:
0
AN:
60080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
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5
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Oct 08, 2024
Athena Diagnostics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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