20-13390456-CAGAG-CAG

Variant names:

• chr20-13390456-CAG-C
• rs745426610
• NM_017714.3:c.1171-6_1171-5delCT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_017714.3(TASP1):​c.1171-6_1171-5delCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,442,464 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TASP1 NM_017714.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.59
• Publications: 0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 20-13390456-CAG-C is Benign according to our data. Variant chr20-13390456-CAG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3055272.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASP1	NM_017714.3	MANE Select	c.1171-6_1171-5delCT		splice_region intron	N/A	NP_060184.2	Q9H6P5-1
	TASP1	NM_001323603.2		c.865-6_865-5delCT		splice_region intron	N/A	NP_001310532.1
	TASP1	NM_001323604.2		c.865-6_865-5delCT		splice_region intron	N/A	NP_001310533.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASP1	ENST00000337743.9	TSL:1 MANE Select	c.1171-6_1171-5delCT		splice_region intron	N/A	ENSP00000338624.4	Q9H6P5-1
	TASP1	ENST00000961261.1		c.1261-6_1261-5delCT		splice_region intron	N/A	ENSP00000631320.1
	TASP1	ENST00000861004.1		c.1171-6_1171-5delCT		splice_region intron	N/A	ENSP00000531063.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151726 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000308 AC: 71 AN: 230312 AF XY: 0.000345

Gnomad AFR exome AF: 0.000331

Gnomad AMR exome AF: 0.000248

Gnomad ASJ exome AF: 0.000318

Gnomad EAS exome AF: 0.0000586

Gnomad FIN exome AF: 0.000877

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000303 AC: 437 AN: 1442464 Hom.: 0 AF XY: 0.000327 AC XY: 235 AN XY: 717662

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000182 AC: 6 AN: 33042

American (AMR) AF: 0.000250 AC: 11 AN: 43956

Ashkenazi Jewish (ASJ) AF: 0.000545 AC: 14 AN: 25690

East Asian (EAS) AF: 0.000335 AC: 13 AN: 38760

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84876

European-Finnish (FIN) AF: 0.000748 AC: 39 AN: 52118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000289 AC: 318 AN: 1098796

Other (OTH) AF: 0.000353 AC: 21 AN: 59508

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000659 AC: 1 AN: 151726 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74064

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00569 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TASP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs745426610; hg19: chr20-13371103; COSMIC: COSV61814857; COSMIC: COSV61814857;