NM_017714.3:c.589A>G

Variant names:

• chr20-13559094-T-C
• NM_017714.3:c.589A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017714.3(TASP1):​c.589A>G​(p.Lys197Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,427,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TASP1 NM_017714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.589A>G	p.Lys197Glu	missense	Exon 8 of 14	NP_060184.2	Q9H6P5-1
	TASP1	NM_001323603.2		c.283A>G	p.Lys95Glu	missense	Exon 9 of 15	NP_001310532.1
	TASP1	NM_001323604.2		c.283A>G	p.Lys95Glu	missense	Exon 9 of 15	NP_001310533.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASP1	ENST00000337743.9	TSL:1 MANE Select	c.589A>G	p.Lys197Glu	missense	Exon 8 of 14	ENSP00000338624.4	Q9H6P5-1
	TASP1	ENST00000961261.1		c.589A>G	p.Lys197Glu	missense	Exon 7 of 14	ENSP00000631320.1
	TASP1	ENST00000861004.1		c.589A>G	p.Lys197Glu	missense	Exon 9 of 15	ENSP00000531063.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427412 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 709328

African (AFR) AF: 0.00 AC: 0 AN: 32152

American (AMR) AF: 0.00 AC: 0 AN: 41592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25434

East Asian (EAS) AF: 0.00 AC: 0 AN: 38152

South Asian (SAS) AF: 0.00 AC: 0 AN: 79658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093832

Other (OTH) AF: 0.00 AC: 0 AN: 58766

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.86	L
PhyloP100		6.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.45
Sift	Benign	0.083	T
Sift4G	Benign	0.24	T
Polyphen		0.056	B
Vest4		0.80
MutPred		0.46		Loss of methylation at K197 (P = 0.0027)
MVP		0.70
MPC		0.76
ClinPred		0.78	D
GERP RS		5.6
Varity_R		0.57
gMVP		0.72
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

hg19: chr20-13539741;