dbSNP rs368102077: TASP1:p.Thr188Ile (chr20-13569512-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017714.3(TASP1):c.563C>T(p.Thr188Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,611,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TASP1
NM_017714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

Publications

1 publications found

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]

TASP1 Gene-Disease associations (from GenCC):

Suleiman-El-Hattab syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

TASP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13582036).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TASP1	NM_017714.3	MANE Select	c.563C>T	p.Thr188Ile	missense	Exon 7 of 14	NP_060184.2	Q9H6P5-1
TASP1	NM_001323603.2		c.257C>T	p.Thr86Ile	missense	Exon 8 of 15	NP_001310532.1
TASP1	NM_001323604.2		c.257C>T	p.Thr86Ile	missense	Exon 8 of 15	NP_001310533.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TASP1	ENST00000337743.9	TSL:1 MANE Select	c.563C>T	p.Thr188Ile	missense	Exon 7 of 14	ENSP00000338624.4	Q9H6P5-1
TASP1	ENST00000961261.1		c.563C>T	p.Thr188Ile	missense	Exon 6 of 14	ENSP00000631320.1
TASP1	ENST00000861004.1		c.563C>T	p.Thr188Ile	missense	Exon 8 of 15	ENSP00000531063.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

249520

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1459608

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.0000671

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.00

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111264

Other (OTH)

AF:

0.00

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41358

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67914

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000562

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.41

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.58

MutationAssessor

Benign

-1.0

PhyloP100

4.9

PrimateAI

Uncertain

0.77

PROVEAN

Benign

2.3

REVEL

Uncertain

0.32

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.40

MVP

0.093

MPC

0.56

ClinPred

0.079

GERP RS

4.9

Varity_R

0.23

gMVP

0.47

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over