20-13569524-G-A

Position:

• chr20-13569524-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017714.3(TASP1):​c.551C>T​(p.Pro184Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TASP1 NM_017714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77

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/exons	MANE	UniProt
TASP1	NM_017714.3	c.551C>T	p.Pro184Leu	missense_variant	7/14	ENST00000337743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASP1	ENST00000337743.9	c.551C>T	p.Pro184Leu	missense_variant	7/14	1	NM_017714.3	P1
TASP1	ENST00000455532.5	c.482C>T	p.Pro161Leu	missense_variant	6/10	5
TASP1	ENST00000480436.5	n.635C>T		non_coding_transcript_exon_variant	7/14	5
TASP1	ENST00000465381.5	n.572+11373C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.551C>T (p.P184L) alteration is located in exon 7 (coding exon 6) of the TASP1 gene. This alteration results from a C to T substitution at nucleotide position 551, causing the proline (P) at amino acid position 184 to be replaced by a leucine (L). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D;D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.085	T;.
Polyphen		0.65	P;B
Vest4		0.46
MutPred		0.46		Gain of catalytic residue at P184 (P = 0.0257);.;
MVP		0.43
MPC		0.98
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.32
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13550171;