rs201338900
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PVS1BS2_Supporting
The NM_198994.3(TGM6):c.691C>T(p.Arg231Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,612,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_198994.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM6 | NM_198994.3 | c.691C>T | p.Arg231Ter | stop_gained | 6/13 | ENST00000202625.7 | |
TGM6 | NM_001254734.2 | c.691C>T | p.Arg231Ter | stop_gained | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM6 | ENST00000202625.7 | c.691C>T | p.Arg231Ter | stop_gained | 6/13 | 1 | NM_198994.3 | P1 | |
TGM6 | ENST00000381423.1 | c.691C>T | p.Arg231Ter | stop_gained | 6/12 | 1 | |||
TGM6 | ENST00000477505.1 | n.322C>T | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251170Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135802
GnomAD4 exome AF: 0.000159 AC: 232AN: 1460790Hom.: 0 Cov.: 32 AF XY: 0.000168 AC XY: 122AN XY: 726662
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 07, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2023 | This premature translational stop signal has been observed in individual(s) with cerebellar ataxia (PMID: 35401678). ClinVar contains an entry for this variant (Variation ID: 437001). 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. This variant is present in population databases (rs201338900, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg231*) in the TGM6 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TGM6 cause disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2019 | - - |
Spinocerebellar ataxia type 35 Pathogenic:1
Pathogenic, no assertion criteria provided | research | O&I group, Department of Genetics, University Medical Center of Groningen | Jul 22, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 15, 2016 | - - |
Polyneuropathy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institute of Human Genetics, University of Wuerzburg | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at