20-13417495-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017714.3(TASP1):​c.1123G>A​(p.Glu375Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TASP1
NM_017714.3 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.85
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TASP1NM_017714.3 linkuse as main transcriptc.1123G>A p.Glu375Lys missense_variant 13/14 ENST00000337743.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TASP1ENST00000337743.9 linkuse as main transcriptc.1123G>A p.Glu375Lys missense_variant 13/141 NM_017714.3 P1Q9H6P5-1
TASP1ENST00000480436.5 linkuse as main transcriptn.1194G>A non_coding_transcript_exon_variant 13/145

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461850
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 06, 2021The c.1123G>A (p.E375K) alteration is located in exon 13 (coding exon 12) of the TASP1 gene. This alteration results from a G to A substitution at nucleotide position 1123, causing the glutamic acid (E) at amino acid position 375 to be replaced by a lysine (K). 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
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Benign
0.090
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.062
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.098
D
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.0
N
REVEL
Uncertain
0.59
Sift
Benign
0.36
T
Sift4G
Benign
0.54
T
Polyphen
0.048
B
Vest4
0.94
MutPred
0.69
Gain of methylation at E375 (P = 0.0139);
MVP
0.76
MPC
0.61
ClinPred
0.91
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.83

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.

Other links and lift over

dbSNP: rs1568772197; hg19: chr20-13398142; API