11-126269213-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001425168.1(FOXRED1):c.-407C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001425168.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250200Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135592
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1460778Hom.: 0 Cov.: 37 AF XY: 0.0000261 AC XY: 19AN XY: 726770
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:2
p.Arg3Trp (CGG>TGG):c.7 C>T in exon 1 of the FOXRED1 gene (NM_017547.3). The R3W missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a positively charged Arginine residue is replaced by an uncharged Tryptophan residue. This change occurs at a position in the FOXRED1 protein that is not highly conserved, and multiple in-silico analyes predict that R3W is a benign sequence change. Therefore, based on the currently available information, it is unclear whether R3W is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). -
Variant summary: FOXRED1 c.7C>T (p.Arg3Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 250200 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7C>T has been reported in the literature in an individual affected with ataxia (Ngo_2020). This report does not provide unequivocal conclusions about association of the variant with Leigh Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at