rs62619919
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006214.4(PHYH):c.734G>A(p.Arg245Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,613,820 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R245W) has been classified as Uncertain significance.
Frequency
Consequence
NM_006214.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHYH | NM_006214.4 | c.734G>A | p.Arg245Gln | missense_variant | 7/9 | ENST00000263038.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.734G>A | p.Arg245Gln | missense_variant | 7/9 | 1 | NM_006214.4 | P1 | |
PHYH | ENST00000396920.7 | c.683G>A | p.Arg228Gln | missense_variant | 7/9 | 5 | |||
PHYH | ENST00000396913.6 | c.434G>A | p.Arg145Gln | missense_variant | 6/8 | 5 | |||
PHYH | ENST00000453759.6 | c.434G>A | p.Arg145Gln | missense_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00696 AC: 1058AN: 152000Hom.: 12 Cov.: 31
GnomAD3 exomes AF: 0.00761 AC: 1914AN: 251492Hom.: 19 AF XY: 0.00834 AC XY: 1134AN XY: 135922
GnomAD4 exome AF: 0.00730 AC: 10671AN: 1461702Hom.: 70 Cov.: 32 AF XY: 0.00763 AC XY: 5547AN XY: 727176
GnomAD4 genome ? AF: 0.00695 AC: 1057AN: 152118Hom.: 12 Cov.: 31 AF XY: 0.00791 AC XY: 588AN XY: 74348
ClinVar
Submissions by phenotype
Phytanic acid storage disease Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | South Asian population allele frequency is 1.166% (rs62619919, 389/30616 alleles, 6 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PHYH: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2020 | This variant is associated with the following publications: (PMID: 14974078, 10767344, 27229527, 27535533) - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 08, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Nonsyndromic cleft lip palate Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Mar 27, 2016 | - - |
Vitamin D-dependent rickets type II with alopecia Benign:1
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The p.Arg245Gln variant in PHYH has been identified in cis with p.Asp177Gly and in 4 individuals with Refsum disease, including 2 homozygotes and 2 heterozygotes (PMID: 10767344), and has been identified in >2% of European (Finnish) chromosomes and 9 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Arg245Gln variant may not impact protein function (PMID: 10767344). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive Refsum disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at