rs923055223

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_017714.3(TASP1):ā€‹c.1024G>Cā€‹(p.Gly342Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

TASP1
NM_017714.3 missense

Scores

15
3
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.75
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TASP1NM_017714.3 linkc.1024G>C p.Gly342Arg missense_variant Exon 12 of 14 ENST00000337743.9 NP_060184.2 Q9H6P5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TASP1ENST00000337743.9 linkc.1024G>C p.Gly342Arg missense_variant Exon 12 of 14 1 NM_017714.3 ENSP00000338624.4 Q9H6P5-1
TASP1ENST00000465381.5 linkn.921G>C non_coding_transcript_exon_variant Exon 10 of 10 5
TASP1ENST00000480436.5 linkn.1095G>C non_coding_transcript_exon_variant Exon 12 of 14 5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
152126
Hom.:
0
Cov.:
32
FAILED QC
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
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.49
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.91
D
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D
M_CAP
Pathogenic
0.43
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-6.2
D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.92
MutPred
0.93
Loss of catalytic residue at V343 (P = 0.0652);
MVP
0.89
MPC
1.6
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.94
gMVP
0.96

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: chr20-13415763; API