rs76079086
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020810.3(TRMT5):c.535C>G(p.His179Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H179N) has been classified as Likely benign.
Frequency
Consequence
NM_020810.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRMT5 | NM_020810.3 | c.535C>G | p.His179Asp | missense_variant | 2/5 | ENST00000261249.7 | |
TRMT5 | NM_001350253.1 | c.619C>G | p.His207Asp | missense_variant | 2/5 | ||
TRMT5 | NM_001350254.1 | c.616C>G | p.His206Asp | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRMT5 | ENST00000261249.7 | c.535C>G | p.His179Asp | missense_variant | 2/5 | 1 | NM_020810.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251410Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135880
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727222
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1509863). This variant has not been reported in the literature in individuals affected with TRMT5-related conditions. This variant is present in population databases (rs76079086, gnomAD 0.06%). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 179 of the TRMT5 protein (p.His179Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at