14-89962826-T-C

Position:

• chr14-89962826-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018319.4(TDP1):​c.-7-282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 740,712 control chromosomes in the GnomAD database, including 7,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (5343 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2248 hom.)
• Consequence: TDP1 NM_018319.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 14-89962826-T-C is Benign according to our data. Variant chr14-89962826-T-C is described in ClinVar as [Benign]. Clinvar id is 1287106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP1	NM_018319.4	c.-7-282T>C		intron_variant		ENST00000335725.9	NP_060789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP1	ENST00000335725.9	c.-7-282T>C		intron_variant		1	NM_018319.4	ENSP00000337353	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26430 AN: 151814 Hom.: 5320 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0513 AC: 30225 AN: 588780 Hom.: 2248 AF XY: 0.0507 AC XY: 13980 AN XY: 275750

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.0947

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.0389

Gnomad4 OTH exome AF: 0.0748

GnomAD4 genome AF: 0.174 AC: 26507 AN: 151932 Hom.: 5343 Cov.: 32 AF XY: 0.169 AC XY: 12517 AN XY: 74262

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0389 Hom.: 94

Bravo AF: 0.194

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs7143875; hg19: chr14-90429170;