chr10-13278279-A-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006214.4(PHYH):c.*22T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,569,420 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 21 hom. )
Consequence
PHYH
NM_006214.4 3_prime_UTR
NM_006214.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0660
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 10-13278279-A-C is Benign according to our data. Variant chr10-13278279-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 299242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00346 (527/152318) while in subpopulation NFE AF= 0.00601 (409/68042). AF 95% confidence interval is 0.00553. There are 5 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHYH | NM_006214.4 | c.*22T>G | 3_prime_UTR_variant | 9/9 | ENST00000263038.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.*22T>G | 3_prime_UTR_variant | 9/9 | 1 | NM_006214.4 | P1 | ||
PHYH | ENST00000396913.6 | c.*22T>G | 3_prime_UTR_variant | 8/8 | 5 | ||||
PHYH | ENST00000396920.7 | c.*22T>G | 3_prime_UTR_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00346 AC: 527AN: 152200Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.00293 AC: 737AN: 251312Hom.: 1 AF XY: 0.00293 AC XY: 398AN XY: 135858
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GnomAD4 exome AF: 0.00275 AC: 3890AN: 1417102Hom.: 21 Cov.: 26 AF XY: 0.00277 AC XY: 1964AN XY: 707994
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GnomAD4 genome AF: 0.00346 AC: 527AN: 152318Hom.: 5 Cov.: 33 AF XY: 0.00364 AC XY: 271AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Phytanic acid storage disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at