NM_001330588.2:c.30C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001330588.2(TPP2):​c.30C>T​(p.Phe10Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TPP2
NM_001330588.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96

Publications

0 publications found
Variant links:
Genes affected
TPP2 (HGNC:12016): (tripeptidyl peptidase 2) This gene encodes a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. The protein has a specialized function that is essential for some MHC class I antigen presentation. The protein is a high molecular mass serine exopeptidase; the amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class rather than the trypsin class. [provided by RefSeq, Jul 2008]
TPP2 Gene-Disease associations (from GenCC):
  • immunodeficiency 78 with autoimmunity and developmental delay
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.19).
BP6
Variant 13-102597068-C-T is Benign according to our data. Variant chr13-102597068-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1099505.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.96 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000722 (11/152326) while in subpopulation AFR AF = 0.00024 (10/41592). AF 95% confidence interval is 0.00013. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPP2NM_001330588.2 linkc.30C>T p.Phe10Phe synonymous_variant Exon 1 of 30 ENST00000376052.5 NP_001317517.1 P29144Q5VZU9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPP2ENST00000376052.5 linkc.30C>T p.Phe10Phe synonymous_variant Exon 1 of 30 5 NM_001330588.2 ENSP00000365220.3 Q5VZU9

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.0000121
AC:
3
AN:
247814
AF XY:
0.00000742
show subpopulations
Gnomad AFR exome
AF:
0.000191
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1459794
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726204
show subpopulations
African (AFR)
AF:
0.000390
AC:
13
AN:
33344
American (AMR)
AF:
0.00
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39648
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86156
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53296
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4802
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111546
Other (OTH)
AF:
0.00
AC:
0
AN:
60222
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000722
AC:
11
AN:
152326
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.000240
AC:
10
AN:
41592
American (AMR)
AF:
0.00
AC:
0
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.000473
AC:
1
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.0000718

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency Benign:1
Jul 21, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.19
CADD
Benign
14
DANN
Benign
0.95
PhyloP100
2.0
PromoterAI
-0.0030
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

Other links and lift over

dbSNP: rs146085226; hg19: chr13-103249418; API