chr16-28844008-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003321.5(TUFM):c.1016G>A(p.Arg339Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,182 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_003321.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUFM | NM_003321.5 | c.1016G>A | p.Arg339Gln | missense_variant | Exon 8 of 10 | ENST00000313511.8 | NP_003312.3 | |
TUFM | NM_001365360.2 | c.932G>A | p.Arg311Gln | missense_variant | Exon 8 of 10 | NP_001352289.1 | ||
MIR4721 | NR_039872.1 | n.-1G>A | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 4 Pathogenic:1
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not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 339 of the TUFM protein (p.Arg339Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of combined oxidative phosphorylation deficiency (PMID: 17160893, 38630895). This variant is also known as R336Q. ClinVar contains an entry for this variant (Variation ID: 7275). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TUFM protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TUFM function (PMID: 17160893, 19524667, 20435138). 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