Variant 14-89989844-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000335725.9(TDP1):c.1366+79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,112,574 control chromosomes in the GnomAD database, including 226,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 37213 hom., cov: 32)

Exomes 𝑓: 0.62 ( 189618 hom. )

Consequence

TDP1
ENST00000335725.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.170

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-89989844-G-T is Benign according to our data. Variant chr14-89989844-G-T is described in ClinVar as [Benign]. Clinvar id is 1278564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP1	NM_018319.4 linkuse as main transcript	c.1366+79G>T		intron_variant		ENST00000335725.9	NP_060789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP1	ENST00000335725.9 linkuse as main transcript	c.1366+79G>T		intron_variant		1	NM_018319.4	ENSP00000337353	P1	Q9NUW8-1

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104343

AN:

151942

Hom.:

37155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.652

GnomAD4 exome

AF:

0.623

AC:

598786

AN:

960514

Hom.:

189618

AF XY:

0.628

AC XY:

312490

AN XY:

497820

show subpopulations

Gnomad4 AFR exome

AF:

0.898

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.760

Gnomad4 FIN exome

AF:

0.652

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.687

AC:

104464

AN:

152060

Hom.:

37213

Cov.:

AF XY:

0.686

AC XY:

51006

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.620

Gnomad4 ASJ

AF:

0.664

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.747

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.653

Alfa

AF:

0.620

Hom.:

14104

Bravo

AF:

0.693

Asia WGS

AF:

0.637

AC:

2218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

DANN

Benign

0.70

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.

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