Variant 20-13534015-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_017714.3(TASP1):c.795+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,609,404 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

TASP1
NM_017714.3 splice_region, intron

Scores

Splicing: ADA: 0.0001110

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.117

Variant links:

Genes affected

TASP1 (HGNC:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TASP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 20-13534015-T-C is Benign according to our data. Variant chr20-13534015-T-C is described in ClinVar as [Benign]. Clinvar id is 3043220.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TASP1	NM_017714.3 linkuse as main transcript	c.795+7A>G		splice_region_variant, intron_variant		ENST00000337743.9	NP_060184.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TASP1	ENST00000337743.9 linkuse as main transcript	c.795+7A>G	splice_region_variant, intron_variant	1	NM_017714.3	ENSP00000338624	P1	Q9H6P5-1
TASP1	ENST00000455532.5 linkuse as main transcript	c.726+7A>G	splice_region_variant, intron_variant	5		ENSP00000400580
TASP1	ENST00000465381.5 linkuse as main transcript	n.692+7A>G	splice_region_variant, intron_variant, non_coding_transcript_variant	5
TASP1	ENST00000480436.5 linkuse as main transcript	n.879+7A>G	splice_region_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

752

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00211

AC:

520

AN:

246876

Hom.:

AF XY:

0.00176

AC XY:

235

AN XY:

133408

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00276

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00158

AC:

2302

AN:

1457180

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1113

AN XY:

724818

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00278

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00499

AC:

760

AN:

152224

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

354

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00559

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TASP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 27, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.7

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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