rs797045100
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006214.4(PHYH):c.766_767del(p.Val256PhefsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
PHYH
NM_006214.4 frameshift
NM_006214.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.21
Genes affected
PHYH (HGNC:8940): (phytanoyl-CoA 2-hydroxylase) This gene is a member of the PhyH family and encodes a peroxisomal protein that is involved in the alpha-oxidation of 3-methyl branched fatty acids. Specifically, this protein converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. Mutations in this gene have been associated with Refsum disease (RD) and deficient protein activity has been associated with Zellweger syndrome and rhizomelic chondrodysplasia punctata. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-13283750-AAC-A is Pathogenic according to our data. Variant chr10-13283750-AAC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208603.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHYH | NM_006214.4 | c.766_767del | p.Val256PhefsTer14 | frameshift_variant | 7/9 | ENST00000263038.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.766_767del | p.Val256PhefsTer14 | frameshift_variant | 7/9 | 1 | NM_006214.4 | P1 | |
PHYH | ENST00000396913.6 | c.466_467del | p.Val156PhefsTer14 | frameshift_variant | 6/8 | 5 | |||
PHYH | ENST00000396920.7 | c.715_716del | p.Val239PhefsTer14 | frameshift_variant | 7/9 | 5 | |||
PHYH | ENST00000453759.6 | c.466_467del | p.Val156PhefsTer14 | frameshift_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Phytanic acid storage disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 12, 2014 | The Val256PhefsX14 variant in PHYH has not been previously identified in the literature or in large population studies. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 256 and lead to a premature termination codon 14 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Complete loss of PHYH function is a known disease mechanism in Refsum disease. In summary, although additional studies are required to fully establish its clinical significance, the Val256PhefsX14 variant is likely pathogenic. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at