6-42964372-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000287.4(PEX6):c.2906G>T(p.Arg969Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R969Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000287.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.2906G>T | p.Arg969Leu | missense_variant | 17/17 | ENST00000304611.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.2906G>T | p.Arg969Leu | missense_variant | 17/17 | 1 | NM_000287.4 | P1 | |
PEX6 | ENST00000244546.4 | c.*442G>T | 3_prime_UTR_variant | 15/15 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250474Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135686
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461508Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727066
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PEX6 protein function. This variant has not been reported in the literature in individuals affected with PEX6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 969 of the PEX6 protein (p.Arg969Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at