10-13278338-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006214.4(PHYH):c.980G>T(p.Arg327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R327Q) has been classified as Likely benign.
Frequency
Consequence
NM_006214.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHYH | NM_006214.4 | c.980G>T | p.Arg327Leu | missense_variant | 9/9 | ENST00000263038.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.980G>T | p.Arg327Leu | missense_variant | 9/9 | 1 | NM_006214.4 | P1 | |
PHYH | ENST00000396920.7 | c.929G>T | p.Arg310Leu | missense_variant | 9/9 | 5 | |||
PHYH | ENST00000396913.6 | c.680G>T | p.Arg227Leu | missense_variant | 8/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251316Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459566Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726298
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 327 of the PHYH protein (p.Arg327Leu). This variant is present in population databases (rs367851769, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PHYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1055584). 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: "Possibly 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