3-33093351-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001039770.3(TMPPE):c.845C>T(p.Thr282Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
TMPPE
NM_001039770.3 missense
NM_001039770.3 missense
Scores
4
9
4
Clinical Significance
Conservation
PhyloP100: 7.93
Genes affected
TMPPE (HGNC:33865): (transmembrane protein with metallophosphoesterase domain) Predicted to enable hydrolase activity and metal ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
GLB1 (HGNC:4298): (galactosidase beta 1) This gene encodes a member of the glycosyl hydrolase 35 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature lysosomal enzyme. This enzyme catalyzes the hydrolysis of a terminal beta-linked galactose residue from ganglioside substrates and other glycoconjugates. Mutations in this gene may result in GM1-gangliosidosis and Morquio B syndrome. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPPE | NM_001039770.3 | c.845C>T | p.Thr282Met | missense_variant | 2/2 | ENST00000342462.5 | |
GLB1 | NM_000404.4 | c.75+3660C>T | intron_variant | ENST00000307363.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPPE | ENST00000342462.5 | c.845C>T | p.Thr282Met | missense_variant | 2/2 | 2 | NM_001039770.3 | P1 | |
GLB1 | ENST00000307363.10 | c.75+3660C>T | intron_variant | 1 | NM_000404.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251394Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135874
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727246
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GnomAD4 genome ? Cov.: 33
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Cov.:
33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.845C>T (p.T282M) alteration is located in exon 2 (coding exon 1) of the TMPPE gene. This alteration results from a C to T substitution at nucleotide position 845, causing the threonine (T) at amino acid position 282 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.57
.;Gain of glycosylation at T282 (P = 0.0359);
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at