rs1211601030
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000359.3(TGM1):c.566delG(p.Gly189fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
TGM1
NM_000359.3 frameshift
NM_000359.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.622
Genes affected
TGM1 (HGNC:11777): (transglutaminase 1) The protein encoded by this gene is a membrane protein that catalyzes the addition of an alkyl group from an akylamine to a glutamine residue of a protein, forming an alkylglutamine in the protein. This protein alkylation leads to crosslinking of proteins and catenation of polyamines to proteins. This gene contains either one or two copies of a 22 nt repeat unit in its 3' UTR. Mutations in this gene have been associated with autosomal recessive lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-24260640-GC-G is Pathogenic according to our data. Variant chr14-24260640-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 2914902.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.566delG | p.Gly189fs | frameshift_variant | 4/15 | ENST00000206765.11 | NP_000350.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.566delG | p.Gly189fs | frameshift_variant | 4/15 | 1 | NM_000359.3 | ENSP00000206765.6 | ||
TGM1 | ENST00000544573.5 | c.-29+1486delG | intron_variant | 2 | ENSP00000439446.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251386Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
GnomAD3 exomes
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135898
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GnomAD4 exome Cov.: 32
GnomAD4 exome
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32
GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | This sequence change creates a premature translational stop signal (p.Gly189Alafs*17) in the TGM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGM1 are known to be pathogenic (PMID: 18948357, 19241467). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TGM1-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at