NM_002637.4(PHKA1):c.1657C>T (p.Arg553Cys) AND Glycogen storage disease IXd

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 24, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002629560.2

Allele description [Variation Report for NM_002637.4(PHKA1):c.1657C>T (p.Arg553Cys)]

NM_002637.4(PHKA1):c.1657C>T (p.Arg553Cys)

Gene:

PHKA1:phosphorylase kinase regulatory subunit alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_002637.4(PHKA1):c.1657C>T (p.Arg553Cys)

HGVS:

NC_000023.11:g.72635212G>A
NG_016599.2:g.83970C>T
NM_001122670.2:c.1657C>T
NM_001172436.2:c.1657C>T
NM_002637.4:c.1657C>TMANE SELECT
NP_001116142.1:p.Arg553Cys
NP_001165907.1:p.Arg553Cys
NP_002628.2:p.Arg553Cys
NC_000023.10:g.71855062G>A

Protein change:

R553C

Molecular consequence:

NM_001122670.2:c.1657C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001172436.2:c.1657C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002637.4:c.1657C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease IXd (GSD9D)
Synonyms:: GSD IXd
Identifiers:: MONDO: MONDO:0010362; MedGen: C1845151; Orphanet: 715; OMIM: 300559

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003521798	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29667327, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003521798

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Novel West syndrome candidate genes in a Chinese cohort.

Peng J, Wang Y, He F, Chen C, Wu LW, Yang LF, Ma YP, Zhang W, Shi ZQ, Chen C, Xia K, Guo H, Yin F, Pang N.

CNS Neurosci Ther. 2018 Dec;24(12):1196-1206. doi: 10.1111/cns.12860. Epub 2018 Apr 17.

PubMed [citation]

PMID:: 29667327
PMCID:: PMC6489871

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003521798.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 553 of the PHKA1 protein (p.Arg553Cys). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This missense change has been observed in individual(s) with clinical features of PHKA1-related conditions (PMID: 29667327). This variant is present in population databases (rs782021325, gnomAD 0.006%).

#	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: Feb 20, 2024

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