NM_000035.4(ALDOB):c.964G>T (p.Glu322Ter) AND Hereditary fructosuria

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 29, 2024
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:: RCV000667914.3

Allele description [Variation Report for NM_000035.4(ALDOB):c.964G>T (p.Glu322Ter)]

NM_000035.4(ALDOB):c.964G>T (p.Glu322Ter)

Gene:

ALDOB:aldolase, fructose-bisphosphate B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q31.1

Genomic location:

Preferred name:

NM_000035.4(ALDOB):c.964G>T (p.Glu322Ter)

HGVS:

NC_000009.12:g.101424878C>A
NG_012387.1:g.15903G>T
NM_000035.4:c.964G>TMANE SELECT
NP_000026.2:p.Glu322Ter
LRG_1244t1:c.964G>T
LRG_1244:g.15903G>T
LRG_1244p1:p.Glu322Ter
NC_000009.11:g.104187160C>A
NM_000035.3:c.964G>T

Protein change:

E322*

Links:

dbSNP: rs1172384674

NCBI 1000 Genomes Browser:

rs1172384674

Molecular consequence:

NM_000035.4:c.964G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary fructosuria
Synonyms:: Hereditary fructose intolerance; Fructose-1-phosphate aldolase deficiency; Aldolase B deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009249; MedGen: C0016751; Orphanet: 469; OMIM: 229600; Human Phenotype Ontology: HP:0005973

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792439	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jun 23, 2017)	unknown	clinical testing	Citation Link,
SCV004393316	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 1856829, 2336380, 12205126, 15880727, 18541450, 19768653, 23430936, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000792439

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Jun 23, 2017)

unknown

clinical testing

Citation Link,

SCV004393316

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 2024)

germline

clinical testing

PubMed (8)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aldolase B mutations in Italian families affected by hereditary fructose intolerance.

Sebastio G, de Franchis R, Strisciuglio P, Andria G, Dionisi Vici C, Sabetta G, Gatti R, Cross NC, Cox TM.

J Med Genet. 1991 Apr;28(4):241-3.

PubMed [citation]

PMID:: 1856829
PMCID:: PMC1016824

A new aldolase B variant, N334K, is a common cause of hereditary fructose intolerance in Yugoslavia.

Cross NC, Stojanov LM, Cox TM.

Nucleic Acids Res. 1990 Apr 11;18(7):1925. No abstract available.

PubMed [citation]

PMID:: 2336380
PMCID:: PMC330648

See all PubMed Citations (8)

Details of each submission

From Counsyl, SCV000792439.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004393316.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Glu322*) in the ALDOB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 43 amino acid(s) of the ALDOB protein. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ALDOB-related conditions. ClinVar contains an entry for this variant (Variation ID: 552618). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the ALDOB protein in which other variant(s) (p.Asn335Lys) have been determined to be pathogenic (PMID: 1856829, 2336380, 12205126, 15880727, 18541450, 19768653, 23430936). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine