dbSNP rs4143999: TDP1:c.-536G>A (chr14-89955149-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000554976.5(TDP1):n.-759G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 157,512 control chromosomes in the GnomAD database, including 2,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2709 hom., cov: 33)

Exomes 𝑓: 0.11 ( 52 hom. )

Consequence

TDP1
ENST00000554976.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.934

Publications

10 publications found

Variant links:

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 1
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

TDP1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000554976.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP1	ENST00000554976.5	TSL:2	n.-759G>A		non_coding_transcript_exon	Exon 1 of 18	ENSP00000452042.1	G3V4W8
	TDP1	ENST00000554976.5	TSL:2	n.-759G>A		5_prime_UTR	Exon 1 of 18	ENSP00000452042.1	G3V4W8

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23619

AN:

152092

Hom.:

2700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.109

AC:

577

AN:

5302

Hom.:

Cov.:

AF XY:

0.118

AC XY:

356

AN XY:

3026

show subpopulations

African (AFR)

AF:

0.161

AC:

AN:

American (AMR)

AF:

0.230

AC:

AN:

174

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.173

AC:

AN:

South Asian (SAS)

AF:

0.201

AC:

271

AN:

1348

European-Finnish (FIN)

AF:

0.0747

AC:

AN:

174

Middle Eastern (MID)

AF:

0.0500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0639

AC:

201

AN:

3146

Other (OTH)

AF:

0.0977

AC:

AN:

266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.156

AC:

23680

AN:

152210

Hom.:

2709

Cov.:

AF XY:

0.160

AC XY:

11910

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.304

AC:

12604

AN:

41516

American (AMR)

AF:

0.213

AC:

3259

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3470

East Asian (EAS)

AF:

0.201

AC:

1043

AN:

5182

South Asian (SAS)

AF:

0.218

AC:

1050

AN:

4820

European-Finnish (FIN)

AF:

0.0759

AC:

805

AN:

10606

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4333

AN:

68006

Other (OTH)

AF:

0.138

AC:

291

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

948

1896

2845

3793

4741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

1816

Bravo

AF:

0.172

Asia WGS

AF:

0.231

AC:

802

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.1

(source)

DANN

Benign

0.88

PhyloP100

-0.93

PromoterAI

-0.018

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over