Variant 14-89956787-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018319.4(TDP1):c.-21C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,300 control chromosomes in the GnomAD database, including 724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 724 hom., cov: 33)

Exomes 𝑓: 0.051 ( 0 hom. )

Consequence

TDP1
NM_018319.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.637

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-89956787-C-T is Benign according to our data. Variant chr14-89956787-C-T is described in ClinVar as [Benign]. Clinvar id is 314821.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-89956787-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP1	NM_018319.4 linkuse as main transcript	c.-21C>T		5_prime_UTR_variant	2/17	ENST00000335725.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP1	ENST00000335725.9 linkuse as main transcript	c.-21C>T		5_prime_UTR_variant	2/17	1	NM_018319.4	P1	Q9NUW8-1

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11168

AN:

152102

Hom.:

719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0757

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0641

Gnomad OTH

AF:

0.0798

GnomAD4 exome

AF:

0.0513

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0517

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.0735

AC:

11194

AN:

152222

Hom.:

724

Cov.:

AF XY:

0.0810

AC XY:

6032

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.218

Gnomad4 FIN

AF:

0.0757

Gnomad4 NFE

AF:

0.0641

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0689

Hom.:

Bravo

AF:

0.0788

Asia WGS

AF:

0.211

AC:

732

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.1

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over