dbSNP rs764843924: TASP1:p.Met214Lys (chr20-13559042-A-T) – 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.641T>A(p.Met214Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000307 in 1,596,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TASP1
NM_017714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 3.84

Publications

0 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

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=0.09294891).

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.641T>A	p.Met214Lys	missense	Exon 8 of 14	NP_060184.2	Q9H6P5-1
TASP1	NM_001323603.2		c.335T>A	p.Met112Lys	missense	Exon 9 of 15	NP_001310532.1
TASP1	NM_001323604.2		c.335T>A	p.Met112Lys	missense	Exon 9 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.641T>A	p.Met214Lys	missense	Exon 8 of 14	ENSP00000338624.4	Q9H6P5-1
TASP1	ENST00000961261.1		c.641T>A	p.Met214Lys	missense	Exon 7 of 14	ENSP00000631320.1
TASP1	ENST00000861004.1		c.641T>A	p.Met214Lys	missense	Exon 9 of 15	ENSP00000531063.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000411

AC:

AN:

243330

AF XY:

0.0000380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.000603

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1444650

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

718192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32988

American (AMR)

AF:

0.00

AC:

AN:

43262

Ashkenazi Jewish (ASJ)

AF:

0.000465

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

38796

South Asian (SAS)

AF:

0.00

AC:

AN:

82812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000218

AC:

AN:

1103022

Other (OTH)

AF:

0.000101

AC:

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000113

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

TASP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.64

M_CAP

Benign

0.038

MetaRNN

Benign

0.093

MetaSVM

Benign

-0.58

MutationAssessor

Benign

-0.97

PhyloP100

3.8

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.43

REVEL

Benign

0.25

Sift

Benign

0.30

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.36

MutPred

0.45

Gain of methylation at M214 (P = 0.0098)

MVP

0.22

MPC

0.81

ClinPred

0.067

GERP RS

5.6

Varity_R

0.43

gMVP

0.52

Mutation Taster

=77/23

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