chr13-102597111-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS1_Supporting
The NM_001330588.2(TPP2):c.73T>G(p.Ser25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,611,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S25C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330588.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPP2 | NM_001330588.2 | c.73T>G | p.Ser25Ala | missense_variant | 1/30 | ENST00000376052.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPP2 | ENST00000376052.5 | c.73T>G | p.Ser25Ala | missense_variant | 1/30 | 5 | NM_001330588.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152070Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000573 AC: 14AN: 244482Hom.: 0 AF XY: 0.0000449 AC XY: 6AN XY: 133504
GnomAD4 exome AF: 0.000263 AC: 384AN: 1458960Hom.: 2 Cov.: 31 AF XY: 0.000262 AC XY: 190AN XY: 725744
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152070Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74294
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2023 | The c.73T>G (p.S25A) alteration is located in exon 1 (coding exon 1) of the TPP2 gene. This alteration results from a T to G substitution at nucleotide position 73, causing the serine (S) at amino acid position 25 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 25 of the TPP2 protein (p.Ser25Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TPP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 854994). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at