rs146025917
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000287.4(PEX6):āc.1081A>Gā(p.Thr361Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T361I) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.1081A>G | p.Thr361Ala | missense_variant | 3/17 | ENST00000304611.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.1081A>G | p.Thr361Ala | missense_variant | 3/17 | 1 | NM_000287.4 | P1 | |
PEX6 | ENST00000244546.4 | c.1081A>G | p.Thr361Ala | missense_variant | 3/15 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152194Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251458Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135896
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727210
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152312Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13AN XY: 74480
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 4A (Zellweger);C3553937:Peroxisome biogenesis disorder 4B;C4225267:Heimler syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 09, 2021 | - - |
Zellweger spectrum disorders Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Peroxisome biogenesis disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 361 of the PEX6 protein (p.Thr361Ala). This variant is present in population databases (rs146025917, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 445406). 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) performed at Invitae indicates that this missense variant is not expected to disrupt PEX6 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 28, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at