Submissions for variant NM_000293.3(PHKB):c.39G>A (p.Trp13Ter)

gnomAD frequency: 0.00217  dbSNP: rs141733590

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000637067	SCV000758515	benign	Glycogen storage disease IXb	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000637067	SCV001279582	benign	Glycogen storage disease IXb	2017-04-27	criteria provided, single submitter	clinical testing	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271542	SCV002556209	benign	not specified	2022-06-28	criteria provided, single submitter	clinical testing	Variant summary: PHKB c.39G>A (p.Trp13X) results in a premature termination codon within the first exon of transcript NM_000293. An alternative transcript (NM_001031835) that is expressed in all tissues has a different initiation site downstream of this variant. The variant allele was found at a frequency of 0.0025 in 274676 control chromosomes (gnomAD), with 4 homozygotes. The variant occurs predominantly at a frequency of 0.014 within the Finnish subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within Finnish control individuals in the gnomAD database is approximately 13 fold of the estimated maximal expected allele frequency for a pathogenic variant in PHKB causing Glycogen Phosphorylase Kinase Deficiency (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Finnish origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV002292574	SCV002585562	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	PHKB: BS1:Supporting, BS2
PreventionGenetics, part of Exact Sciences	RCV003965337	SCV004782619	benign	PHKB-related condition	2022-05-26	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).