NM_000293.3(PHKB):c.8G>C (p.Gly3Ala) AND Glycogen storage disease IXb

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 5, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001121034.6

Allele description [Variation Report for NM_000293.3(PHKB):c.8G>C (p.Gly3Ala)]

NM_000293.3(PHKB):c.8G>C (p.Gly3Ala)

Genes:

LOC130058947:ATAC-STARR-seq lymphoblastoid silent region 7451 [Gene]
PHKB:phosphorylase kinase regulatory subunit beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_000293.3(PHKB):c.8G>C (p.Gly3Ala)

HGVS:

NC_000016.10:g.47461358G>C
NG_016598.1:g.5060G>C
NM_000293.3:c.8G>CMANE SELECT
NM_001031835.3:c.-126G>C
NM_001363837.1:c.8G>C
NP_000284.1:p.Gly3Ala
NP_001350766.1:p.Gly3Ala
NC_000016.9:g.47495269G>C
NC_000016.9:g.47495269G>C
NM_000293.2:c.8G>C

Protein change:

G3A

Links:

dbSNP: rs145047641

NCBI 1000 Genomes Browser:

rs145047641

Molecular consequence:

NM_001031835.3:c.-126G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000293.3:c.8G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363837.1:c.8G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease IXb (GSD9B)
Synonyms:: GLYCOGENOSIS OF LIVER AND MUSCLE, AUTOSOMAL RECESSIVE; GSD IXb; PHOSPHORYLASE KINASE DEFICIENCY OF LIVER AND MUSCLE, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0009868; MedGen: C0543514; Orphanet: 79240; OMIM: 261750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001279580	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	Citation Link,
SCV003263774	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001279580

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

Citation Link,

SCV003263774

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001279580.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003263774.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 3 of the PHKB protein (p.Gly3Ala). This variant is present in population databases (rs145047641, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with PHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 887974). 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: "Tolerated"; 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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