1-165752165-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_019026.6(TMCO1):āc.260G>Cā(p.Arg87Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000661 in 151,210 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 (ā ).
Frequency
Consequence
NM_019026.6 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMCO1 | NM_019026.6 | c.260G>C | p.Arg87Pro | missense_variant | Exon 5 of 7 | ENST00000367881.11 | NP_061899.3 | |
TMCO1 | NM_001256164.1 | c.311G>C | p.Arg104Pro | missense_variant | Exon 5 of 7 | NP_001243093.1 | ||
TMCO1 | NM_001256165.1 | c.224G>C | p.Arg75Pro | missense_variant | Exon 5 of 7 | NP_001243094.1 | ||
TMCO1 | NR_045818.1 | n.354G>C | non_coding_transcript_exon_variant | Exon 5 of 7 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151210Hom.: 0 Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000661 AC: 1AN: 151210Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73736
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 138 of the TMCO1 protein (p.Arg138Pro). 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with TMCO1-related conditions. This variant is not present in population databases (gnomAD no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at