20-13559094-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TASP1	NM_017714.3	c.589A>G	p.Lys197Glu	missense_variant	Exon 8 of 14	ENST00000337743.9	NP_060184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TASP1	ENST00000337743.9	c.589A>G	p.Lys197Glu	missense_variant	Exon 8 of 14	1	NM_017714.3	ENSP00000338624.4
TASP1	ENST00000455532.5	c.520A>G	p.Lys174Glu	missense_variant	Exon 7 of 10	5		ENSP00000400580.1
TASP1	ENST00000480436.5	n.673A>G		non_coding_transcript_exon_variant	Exon 8 of 14	5
TASP1	ENST00000465381.5	n.572+21803A>G		intron_variant	Intron 6 of 9	5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.589A>G (p.K197E) alteration is located in exon 8 (coding exon 7) of the TASP1 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the lysine (K) at amino acid position 197 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.86	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.45
Sift	Benign	0.083	T;T
Sift4G	Benign	0.24	T;.
Polyphen		0.056	B;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13539741;