20-13580985-TA-T

Variant summary

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

The NM_017714.3(TASP1):c.404-5del 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 0.07 in 1,418,182 control chromosomes in the GnomAD database, including 206 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (203 hom., cov: 0)
  • Exomes 𝑓: 0.074 (3 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-TA-T is Benign according to our data. Variant chr20-13580985-TA-T is described in ClinVar as [Benign]. Clinvar id is 3058929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASP1	NM_017714.3	c.404-5del		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.404-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_017714.3	P1
TASP1	ENST00000455532.5	c.335-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
TASP1	ENST00000465381.5	n.488-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
TASP1	ENST00000480436.5	n.488-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4409 AN: 139832 Hom.: 203 Cov.: 0

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.0197

Gnomad EAS AF: 0.00268

Gnomad SAS AF: 0.00278

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0105

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.0288

GnomAD4 exome AF: 0.0742 AC: 94805 AN: 1278306 Hom.: 3 Cov.: 21 AF XY: 0.0763 AC XY: 48591 AN XY: 637070

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0815

Gnomad4 EAS exome AF: 0.0931

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0776

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0850

GnomAD4 genome AF: 0.0316 AC: 4418 AN: 139876 Hom.: 203 Cov.: 0 AF XY: 0.0311 AC XY: 2103 AN XY: 67654

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.0197

Gnomad4 EAS AF: 0.00269

Gnomad4 SAS AF: 0.00280

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.0286

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

Oct 29, 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;