rs12918964
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000293.3(PHKB):c.3121C>T(p.Arg1041Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,518,908 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. R1041Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000293.3 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 |
---|---|---|---|---|---|---|---|
PHKB | NM_000293.3 | c.3121C>T | p.Arg1041Trp | missense_variant | 30/31 | ENST00000323584.10 | |
PHKB | NM_001363837.1 | c.3121C>T | p.Arg1041Trp | missense_variant | 30/31 | ||
PHKB | NM_001031835.3 | c.3100C>T | p.Arg1034Trp | missense_variant | 31/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKB | ENST00000323584.10 | c.3121C>T | p.Arg1041Trp | missense_variant | 30/31 | 1 | NM_000293.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00737 AC: 1044AN: 141718Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00590 AC: 1455AN: 246562Hom.: 14 AF XY: 0.00594 AC XY: 794AN XY: 133692
GnomAD4 exome AF: 0.0109 AC: 15071AN: 1377168Hom.: 105 Cov.: 31 AF XY: 0.0105 AC XY: 7206AN XY: 687628
GnomAD4 genome ? AF: 0.00736 AC: 1043AN: 141740Hom.: 6 Cov.: 32 AF XY: 0.00688 AC XY: 470AN XY: 68314
ClinVar
Submissions by phenotype
Glycogen storage disease IXb Benign:3
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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 27, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | PHKB: BP4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 10, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at