rs751248771
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_018006.5(TRMU):c.40G>A(p.Gly14Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,561,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G14G) has been classified as Likely benign.
Frequency
Consequence
NM_018006.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRMU | NM_018006.5 | c.40G>A | p.Gly14Ser | missense_variant | 1/11 | ENST00000645190.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRMU | ENST00000645190.1 | c.40G>A | p.Gly14Ser | missense_variant | 1/11 | NM_018006.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000431 AC: 7AN: 162286Hom.: 0 AF XY: 0.0000335 AC XY: 3AN XY: 89512
GnomAD4 exome AF: 0.0000121 AC: 17AN: 1409422Hom.: 0 Cov.: 31 AF XY: 0.0000100 AC XY: 7AN XY: 697876
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74362
ClinVar
Submissions by phenotype
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 07, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2020 | Identified as heterozygous in an individual with infantile liver failure, hepatomegaly, current age 5 of years; A second variant was not described (Boczonadi et al., 2015); Analysis in patient cells harboring G14S showed reduced mitochondrial enzymatic activities of Complex I and IV and the 2-thiouridylation levels of the mitochondrial tRNAs were markedly reduced (Zeharia et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19732863, 25407320, 21910628) - |
Aminoglycoside-induced deafness;C3278664:Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 07, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at