NM_001243177.4(ALDOA):c.1141G>A (p.Glu381Lys) AND HNSHA due to aldolase A deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 10, 2023
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:: RCV002628109.7

Allele description [Variation Report for NM_001243177.4(ALDOA):c.1141G>A (p.Glu381Lys)]

NM_001243177.4(ALDOA):c.1141G>A (p.Glu381Lys)

Genes:

ALDOA:aldolase, fructose-bisphosphate A [Gene - OMIM - HGNC]
LOC112694756:uncharaterized LOC112694756 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_001243177.4(ALDOA):c.1141G>A (p.Glu381Lys)

HGVS:

NC_000016.10:g.30070009G>A
NG_008010.1:g.21840G>A
NM_001127617.2:c.979G>A
NM_001243177.4:c.1141G>AMANE SELECT
NM_001365304.2:c.*1488G>AMANE SELECT
NM_001365305.2:c.*1488G>A
NM_001365307.2:c.*1488G>A
NM_184041.5:c.979G>A
NM_184043.2:c.979G>A
NP_001121089.1:p.Glu327Lys
NP_001230106.1:p.Glu381Lys
NP_908930.1:p.Glu327Lys
NP_908932.1:p.Glu327Lys
LRG_1180t1:c.979G>A
LRG_1180t2:c.1141G>A
LRG_1180:g.21840G>A
LRG_1180p1:p.Glu327Lys
LRG_1180p2:p.Glu381Lys
NC_000016.9:g.30081330G>A
NM_184041.4:c.979G>A

Protein change:

E327K

Links:

dbSNP: rs375546208

NCBI 1000 Genomes Browser:

rs375546208

Molecular consequence:

NM_001365304.2:c.*1488G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001365305.2:c.*1488G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001365307.2:c.*1488G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001127617.2:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243177.4:c.1141G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_184041.5:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_184043.2:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: HNSHA due to aldolase A deficiency (GSD12)
Synonyms:: GLYCOGEN STORAGE DISEASE XII; GSD XII; RED CELL ALDOLASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012747; MedGen: C0272066; Orphanet: 57; OMIM: 611881

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003509591	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003823166	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004562720	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Apr 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003509591

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 11, 2022)

germline

clinical testing

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

SCV003823166

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 12, 2021)

germline

clinical testing

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

SCV004562720

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Apr 10, 2023)

germline

clinical testing

Citation Link

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003509591.1

#	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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 327 of the ALDOA protein (p.Glu327Lys). This variant is present in population databases (rs375546208, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with ALDOA-related conditions. 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. 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

From Revvity Omics, Revvity, SCV003823166.3

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

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004562720.1

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

#	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 6, 2025

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