XM_047440269.1:c.1171-15281G>A

Variant names:

• chr20-13331336-C-T
• rs6074591
• XM_047440269.1:c.1171-15281G>A

Variant summary

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

The XM_047440269.1(TASP1):​c.1171-15281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,190 control chromosomes in the GnomAD database, including 1,380 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 0.11 (1380 hom., cov: 32)
• Consequence: TASP1 XM_047440269.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TASP1	XM_047440269.1	c.1171-15281G>A		intron_variant	Intron 13 of 13		XP_047296225.1
TASP1	XR_001754319.3	n.1284-15281G>A		intron_variant	Intron 13 of 14
TASP1	XR_007067463.1	n.1284-15281G>A		intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17231 AN: 152072 Hom.: 1380 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.113 AC: 17231 AN: 152190 Hom.: 1380 Cov.: 32 AF XY: 0.111 AC XY: 8284 AN XY: 74386

African (AFR) AF: 0.0306 AC: 1273 AN: 41546

American (AMR) AF: 0.0859 AC: 1314 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5192

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10568

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11507 AN: 67982

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.143 Hom.: 281

Bravo AF: 0.102

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.72
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6074591; hg19: chr20-13311983; COSMIC: COSV73356183;