20-13534015-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017714.3(TASP1):c.795+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,609,404 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: TASP1 NM_017714.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001110
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 20-13534015-T-C is Benign according to our data. Variant chr20-13534015-T-C is described in ClinVar as [Benign]. Clinvar id is 3043220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASP1	NM_017714.3	c.795+7A>G		splice_region_variant, intron_variant		ENST00000337743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASP1	ENST00000337743.9	c.795+7A>G		splice_region_variant, intron_variant		1	NM_017714.3	P1
TASP1	ENST00000455532.5	c.726+7A>G		splice_region_variant, intron_variant		5
TASP1	ENST00000465381.5	n.692+7A>G		splice_region_variant, intron_variant, non_coding_transcript_variant		5
TASP1	ENST00000480436.5	n.879+7A>G		splice_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 752 AN: 152106 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00211 AC: 520 AN: 246876 Hom.: 2 AF XY: 0.00176 AC XY: 235 AN XY: 133408

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00276

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.00284

GnomAD4 exome AF: 0.00158 AC: 2302 AN: 1457180 Hom.: 5 Cov.: 30 AF XY: 0.00154 AC XY: 1113 AN XY: 724818

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.00205

Gnomad4 ASJ exome AF: 0.00278

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00286

GnomAD4 genome AF: 0.00499 AC: 760 AN: 152224 Hom.: 4 Cov.: 32 AF XY: 0.00476 AC XY: 354 AN XY: 74432

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00390 Hom.: 3

Bravo AF: 0.00559

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00238

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 27, 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	4.7
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0060
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: rs77527408; hg19: chr20-13514662;