Variant 20-13483309-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017714.3(TASP1):c.903A>G(p.Ile301Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,444,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TASP1
NM_017714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20691887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASP1	NM_017714.3 linkuse as main transcript	c.903A>G	p.Ile301Met	missense_variant	11/14	ENST00000337743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASP1	ENST00000337743.9 linkuse as main transcript	c.903A>G	p.Ile301Met	missense_variant	11/14	1	NM_017714.3	P1	Q9H6P5-1
TASP1	ENST00000455532.5 linkuse as main transcript	c.834A>G	p.Ile278Met	missense_variant	10/10	5
TASP1	ENST00000465381.5 linkuse as main transcript	n.800A>G		non_coding_transcript_exon_variant	9/10	5
TASP1	ENST00000480436.5 linkuse as main transcript	n.974A>G		non_coding_transcript_exon_variant	11/14	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000829

AC:

AN:

241204

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1444956

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.903A>G (p.I301M) alteration is located in exon 11 (coding exon 10) of the TASP1 gene. This alteration results from a A to G substitution at nucleotide position 903, causing the isoleucine (I) at amino acid position 301 to be replaced by a methionine (M). 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

0.064

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.40

T;T

Eigen

Benign

0.043

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.8

N;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

1.0

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.45

T;T

Sift4G

Benign

0.39

T;.

Polyphen

0.0040

B;B

Vest4

0.38

MutPred

0.59

Gain of disorder (P = 0.1023);.;

MVP

0.16

MPC

0.53

ClinPred

0.22

GERP RS

5.7

Varity_R

0.54

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over