20-13203604-C-T

Variant names:

• chr20-13203604-C-T
• rs6131447
• XR_001754319.3:n.1370-98347G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_001754319.3(TASP1):​n.1370-98347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,000 control chromosomes in the GnomAD database, including 11,523 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11523 hom., cov: 33)
• Consequence: TASP1 XR_001754319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 2 publications found

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]

TASP1 Gene-Disease associations (from GenCC):

• Suleiman-El-Hattab syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57460 AN: 151882 Hom.: 11508 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57522 AN: 152000 Hom.: 11523 Cov.: 33 AF XY: 0.374 AC XY: 27771 AN XY: 74300

African (AFR) AF: 0.525 AC: 21777 AN: 41460

American (AMR) AF: 0.303 AC: 4638 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1847 AN: 5182

South Asian (SAS) AF: 0.272 AC: 1307 AN: 4814

European-Finnish (FIN) AF: 0.361 AC: 3804 AN: 10530

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22437 AN: 67946

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.337 Hom.: 21957

Bravo AF: 0.379

Asia WGS AF: 0.311 AC: 1078 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.9
DANN	Benign	0.36
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6131447; hg19: chr20-13184251;