rs121434452
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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R339W) has been classified 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUFM | NM_003321.5 | c.1016G>A | p.Arg339Gln | missense_variant | 8/10 | ENST00000313511.8 | |
TUFM | NM_001365360.2 | c.932G>A | p.Arg311Gln | missense_variant | 8/10 | ||
MIR4721 | NR_039872.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUFM | ENST00000313511.8 | c.1016G>A | p.Arg339Gln | missense_variant | 8/10 | 1 | NM_003321.5 | P1 | |
TUFM | ENST00000569217.1 | n.325G>A | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
TUFM | ENST00000565012.1 | c.*543G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 | ||||
MIR4721 | ENST00000577590.1 | upstream_gene_variant |
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
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2007 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2021 | 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. Experimental studies have shown that this missense change affects TUFM function (PMID: 17160893, 19524667, 20435138). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 7275). This variant is also known as R336Q. This missense change has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (PMID: 17160893). This variant is not present in population databases (gnomAD no frequency). 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at