20-13580985-TAA-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_017714.3(TASP1):c.404-6_404-5del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00118 in 1,458,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: TASP1 NM_017714.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.00

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 20-13580985-TAA-T is Benign according to our data. Variant chr20-13580985-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042908.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASP1	NM_017714.3	c.404-6_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.404-6_404-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_017714.3	P1
TASP1	ENST00000455532.5	c.335-6_335-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
TASP1	ENST00000465381.5	n.488-6_488-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
TASP1	ENST00000480436.5	n.488-6_488-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000286 AC: 4 AN: 139906 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00130 AC: 1715 AN: 1318916 Hom.: 0 AF XY: 0.00128 AC XY: 838 AN XY: 657074

Gnomad4 AFR exome AF: 0.00565

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00102

Gnomad4 SAS exome AF: 0.00333

Gnomad4 FIN exome AF: 0.00166

Gnomad4 NFE exome AF: 0.000963

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.0000286 AC: 4 AN: 139906 Hom.: 0 Cov.: 0 AF XY: 0.0000444 AC XY: 3 AN XY: 67632

Gnomad4 AFR AF: 0.0000800

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000122

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TASP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

This variant is classified as likely 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)		0.0		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

Other links and lift over

dbSNP: rs71334133; hg19: chr20-13561632;