Variant 20-13534052-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_017714.3(TASP1):c.765G>A(p.Leu255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,410 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 35 hom. )

Consequence

TASP1
NM_017714.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.04

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 20-13534052-C-T is Benign according to our data. Variant chr20-13534052-C-T is described in ClinVar as [Benign]. Clinvar id is 3033137.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00377 (5502/1461220) while in subpopulation AMR AF= 0.0195 (873/44662). AF 95% confidence interval is 0.0185. There are 35 homozygotes in gnomad4_exome. There are 2730 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TASP1	NM_017714.3 linkuse as main transcript	c.765G>A	p.Leu255=	synonymous_variant	9/14	ENST00000337743.9	NP_060184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TASP1	ENST00000337743.9 linkuse as main transcript	c.765G>A	p.Leu255=	synonymous_variant	9/14	1	NM_017714.3	ENSP00000338624	P1	Q9H6P5-1
TASP1	ENST00000455532.5 linkuse as main transcript	c.696G>A	p.Leu232=	synonymous_variant	8/10	5		ENSP00000400580
TASP1	ENST00000465381.5 linkuse as main transcript	n.662G>A		non_coding_transcript_exon_variant	7/10	5
TASP1	ENST00000480436.5 linkuse as main transcript	n.849G>A		non_coding_transcript_exon_variant	9/14	5

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

492

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00675

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0118

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00519

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00607

AC:

1522

AN:

250782

Hom.:

AF XY:

0.00535

AC XY:

725

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00986

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00332

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00377

AC:

5502

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2730

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.000766

Gnomad4 EAS exome

AF:

0.00799

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00627

Gnomad4 NFE exome

AF:

0.00317

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152190

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00694

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00519

Gnomad4 NFE

AF:

0.00343

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.00351

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00220

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

Nov 12, 2019

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

-0.35

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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