12-88153336-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001366580.1(TMTC3):c.-33C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000616 in 1,461,068 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 (★).
Frequency
Consequence
NM_001366580.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMTC3 | ENST00000266712.11 | c.235C>T | p.Arg79Cys | missense_variant | Exon 3 of 14 | 1 | NM_181783.4 | ENSP00000266712.6 | ||
TMTC3 | ENST00000547034.5 | n.235C>T | non_coding_transcript_exon_variant | Exon 3 of 12 | 1 | ENSP00000448733.1 | ||||
TMTC3 | ENST00000549011.5 | c.235C>T | p.Arg79Cys | missense_variant | Exon 3 of 4 | 4 | ENSP00000447640.1 | |||
TMTC3 | ENST00000551088.1 | c.190-952C>T | intron_variant | Intron 2 of 4 | 3 | ENSP00000448566.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250822Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135624
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461068Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726866
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1482338). This variant has not been reported in the literature in individuals affected with TMTC3-related conditions. This variant is present in population databases (rs768991210, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the TMTC3 protein (p.Arg79Cys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at