rs1182257457
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_012210.4(TRIM32):c.1196C>T(p.Thr399Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T399T) has been classified as Likely benign.
Frequency
Consequence
NM_012210.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM32 | NM_012210.4 | c.1196C>T | p.Thr399Ile | missense_variant | 2/2 | ENST00000450136.2 | |
ASTN2 | NM_001365068.1 | c.2806+26833G>A | intron_variant | ENST00000313400.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM32 | ENST00000450136.2 | c.1196C>T | p.Thr399Ile | missense_variant | 2/2 | 1 | NM_012210.4 | P1 | |
ASTN2 | ENST00000313400.9 | c.2806+26833G>A | intron_variant | 5 | NM_001365068.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251142Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135798
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
TRIM32-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | The TRIM32 c.1196C>T variant is predicted to result in the amino acid substitution p.Thr399Ile. This variant was reported in the heterozygous state in an individual with TRIM32-related myopathies; however, a second variant was not identified (Table S1, Johnson et al. 2019. PubMed ID: 29921608). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-119461217-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 399 of the TRIM32 protein (p.Thr399Ile). 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 TRIM32-related conditions. ClinVar contains an entry for this variant (Variation ID: 531835). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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