X-72611092-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002637.4(PHKA1):c.2462G>A(p.Arg821His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,203,695 control chromosomes in the GnomAD database, including 12 homozygotes. There are 1,647 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R821C) has been classified as Uncertain significance.
Frequency
Consequence
NM_002637.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA1 | NM_002637.4 | c.2462G>A | p.Arg821His | missense_variant | 22/32 | ENST00000373542.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA1 | ENST00000373542.9 | c.2462G>A | p.Arg821His | missense_variant | 22/32 | 1 | NM_002637.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00274 AC: 305AN: 111357Hom.: 2 Cov.: 22 AF XY: 0.00209 AC XY: 70AN XY: 33537
GnomAD3 exomes AF: 0.00331 AC: 605AN: 182660Hom.: 2 AF XY: 0.00316 AC XY: 213AN XY: 67366
GnomAD4 exome AF: 0.00462 AC: 5043AN: 1092285Hom.: 10 Cov.: 28 AF XY: 0.00440 AC XY: 1577AN XY: 358009
GnomAD4 genome AF: 0.00274 AC: 305AN: 111410Hom.: 2 Cov.: 22 AF XY: 0.00208 AC XY: 70AN XY: 33600
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Glycogen storage disease IXd Benign:2
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at