Variant rs1555382978 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000335725.9(TDP1):c.556A>G(p.Lys186Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,658 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TDP1
ENST00000335725.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22931665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP1	NM_018319.4 linkuse as main transcript	c.556A>G	p.Lys186Glu	missense_variant	3/17	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.556A>G	p.Lys186Glu	missense_variant	3/17	1	NM_018319.4	ENSP00000337353	P1	Q9NUW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;T;T;.;T;.

Eigen

Benign

0.083

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.23

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.076

T;T;T;T;T;T

Sift4G

Benign

0.098

T;T;T;T;T;T

Polyphen

0.48

P;.;B;.;B;B

Vest4

0.60

MutPred

0.51

Loss of ubiquitination at K186 (P = 0.0155);Loss of ubiquitination at K186 (P = 0.0155);Loss of ubiquitination at K186 (P = 0.0155);.;Loss of ubiquitination at K186 (P = 0.0155);Loss of ubiquitination at K186 (P = 0.0155);

MVP

0.21

MPC

0.18

ClinPred

0.71

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.64

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