11-126269207-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001425168.1(FOXRED1):c.-413A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000013 in 1,612,502 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_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 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152254Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250192Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135574
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460248Hom.: 0 Cov.: 37 AF XY: 0.00000963 AC XY: 7AN XY: 726530
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152254Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
Mitochondrial complex 1 deficiency, nuclear type 19 Uncertain:1
The start lost was identified in the Hom state in the FOXRED1 gene. This variant leads to p.Met1?. In silico tools predict this variant to be neutral. The conservation at this position is high. The splice prediction at this position is low. This variant has not been seen previously in our laboratory. The variant is present in ClinVar, Other, and absent from HGMD. This variant is reported in gnomAD (MAF 0.00029). This variant is not present in the homozygous state in gnomAD. According to the ACMG guidelines, the variant is classified as VUS (PVS1_sup, PM2_sup, PM3_sup) -
not provided Uncertain:1
This sequence change affects the initiator methionine of the FOXRED1 mRNA. The next in-frame methionine is located at codon 10. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FOXRED1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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