chr20-2394454-AT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_StrongBS2_Supporting
The NM_198994.3(TGM6):βc.11delβ(p.Ile4ThrfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000055 ( 0 hom. )
Consequence
TGM6
NM_198994.3 frameshift
NM_198994.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.860
Genes affected
TGM6 (HGNC:16255): (transglutaminase 6) The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
BS2
High AC in GnomAdExome4 at 8 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM6 | NM_198994.3 | c.11del | p.Ile4ThrfsTer41 | frameshift_variant | 2/13 | ENST00000202625.7 | |
TGM6 | NM_001254734.2 | c.11del | p.Ile4ThrfsTer41 | frameshift_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM6 | ENST00000202625.7 | c.11del | p.Ile4ThrfsTer41 | frameshift_variant | 2/13 | 1 | NM_198994.3 | P1 | |
TGM6 | ENST00000381423.1 | c.11del | p.Ile4ThrfsTer41 | frameshift_variant | 2/12 | 1 | |||
TGM6 | ENST00000477505.1 | n.4del | non_coding_transcript_exon_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248330Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134576
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459126Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725892
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Mar 23, 2020 | ACMG classification criteria: PM2 - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 25, 2019 | - - |
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