20-13580985-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017714.3(TASP1):c.404-5_404-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,397,686 control chromosomes in the GnomAD database, including 115 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (8 hom., cov: 0)
  • Exomes 𝑓: 0.13 (107 hom.)
• Consequence: TASP1 NM_017714.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.41

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-13580985-T-TA is Benign according to our data. Variant chr20-13580985-T-TA is described in ClinVar as [Benign]. Clinvar id is 3059573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASP1	NM_017714.3	c.404-5_404-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000337743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASP1	ENST00000337743.9	c.404-5_404-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_017714.3	P1
TASP1	ENST00000455532.5	c.335-5_335-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
TASP1	ENST00000465381.5	n.488-5_488-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
TASP1	ENST00000480436.5	n.488-5_488-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00656 AC: 917 AN: 139846 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00257

Gnomad ASJ AF: 0.00537

Gnomad EAS AF: 0.00454

Gnomad SAS AF: 0.00509

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.00699

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.00157

GnomAD4 exome AF: 0.131 AC: 165342 AN: 1257798 Hom.: 107 Cov.: 21 AF XY: 0.132 AC XY: 83009 AN XY: 626928

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.00663 AC: 927 AN: 139888 Hom.: 8 Cov.: 0 AF XY: 0.00816 AC XY: 552 AN XY: 67652

Gnomad4 AFR AF: 0.00312

Gnomad4 AMR AF: 0.00271

Gnomad4 ASJ AF: 0.00537

Gnomad4 EAS AF: 0.00455

Gnomad4 SAS AF: 0.00512

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.00156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TASP1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 14, 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs71334133; hg19: chr20-13561632;