20-13580985-T-TAA

Position:

• chr20-13580985-T-TAA

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_404-4insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (9993 hom., cov: 0)
  • Exomes 𝑓: 0.29 (2265 hom.)
  • Failed GnomAD Quality Control
• 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-TAA is Benign according to our data. Variant chr20-13580985-T-TAA is described in ClinVar as [Benign]. Clinvar id is 3059496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.376 AC: 52481 AN: 139594 Hom.: 9992 Cov.: 0

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.364

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.287 AC: 363839 AN: 1268364 Hom.: 2265 Cov.: 21 AF XY: 0.284 AC XY: 179055 AN XY: 631160

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.376 AC: 52488 AN: 139638 Hom.: 9993 Cov.: 0 AF XY: 0.376 AC XY: 25370 AN XY: 67522

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.366

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

Nov 20, 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

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;