rs61752139
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5
The NM_000287.4(PEX6):c.35T>C(p.Phe12Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000775 in 1,419,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. F12F) has been classified as Likely benign.
Frequency
Consequence
NM_000287.4 missense
Scores
Clinical Significance
Conservation
Publications
- peroxisome biogenesis disorderInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- peroxisome biogenesis disorder 4A (Zellweger)Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
- peroxisome biogenesis disorder 4BInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- Heimler syndrome 2Inheritance: AR Classification: MODERATE Submitted by: G2P
- autosomal recessive cerebellar ataxia-blindness-deafness syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Zellweger spectrum disordersInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.35T>C | p.Phe12Ser | missense_variant | Exon 1 of 17 | ENST00000304611.13 | NP_000278.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00 AC: 0AN: 185122 AF XY: 0.00
GnomAD4 exome AF: 0.00000775 AC: 11AN: 1419642Hom.: 0 Cov.: 35 AF XY: 0.00000568 AC XY: 4AN XY: 704162 show subpopulations
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74342 show subpopulations
ClinVar
Submissions by phenotype
Heimler syndrome 2 Pathogenic:1
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Peroxisome biogenesis disorder 4A (Zellweger);C3553937:Peroxisome biogenesis disorder 4B Uncertain:1
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
Peroxisome biogenesis disorder Uncertain:1
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 12 of the PEX6 protein (p.Phe12Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Zellweger spectrum disorder (PMID: 15542397). ClinVar contains an entry for this variant (Variation ID: 557609). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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