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NM_001698.3(AUH):c.824C>T (p.Ala275Val) AND not provided

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jul 25, 2014
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:
RCV000196487.8

Allele description [Variation Report for NM_001698.3(AUH):c.824C>T (p.Ala275Val)]

NM_001698.3(AUH):c.824C>T (p.Ala275Val)

Gene:
AUH:AU RNA binding methylglutaconyl-CoA hydratase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.31
Genomic location:
Preferred name:
NM_001698.3(AUH):c.824C>T (p.Ala275Val)
Other names:
p.A275V:GCG>GTG
HGVS:
  • NC_000009.12:g.91220824G>A
  • NG_008017.1:g.146101C>T
  • NM_001306190.2:c.737C>T
  • NM_001351431.2:c.497C>T
  • NM_001351432.2:c.497C>T
  • NM_001351433.2:c.497C>T
  • NM_001698.3:c.824C>TMANE SELECT
  • NP_001293119.1:p.Ala246Val
  • NP_001338360.1:p.Ala166Val
  • NP_001338361.1:p.Ala166Val
  • NP_001338362.1:p.Ala166Val
  • NP_001689.1:p.Ala275Val
  • NP_001689.1:p.Ala275Val
  • LRG_449t1:c.824C>T
  • LRG_449:g.146101C>T
  • LRG_449p1:p.Ala275Val
  • NC_000009.11:g.93983106G>A
  • NM_001698.2:c.824C>T
Protein change:
A166V
Links:
dbSNP: rs748318386
NCBI 1000 Genomes Browser:
rs748318386
Molecular consequence:
  • NM_001306190.2:c.737C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351431.2:c.497C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351432.2:c.497C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351433.2:c.497C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001698.3:c.824C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000251181GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Jul 25, 2014) 		germlineclinical testing

Citation Link,

SCV000802707Mayo Clinic Laboratories, Mayo Clinic
no assertion criteria provided
Uncertain significance
(May 14, 2024) 		unknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000251181.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

p.Ala275Val (GCG>GTG): c.824 C>T in exon 7 of the AUH gene (NM_001698.2). A c.824 C>T sequence change likely associated with 3-methylglutaconic aciduria type 1 was identified in the AUH gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. If the protein was transcribed normally, this would lead to the replacement of an Alanine codon (GCG) with a Valine codon (GTG) at amino acid position 275. However, the c.824 C>T nucleotide substitution most likely appears to result in an error in gene splicing. This substitution occurs 21 nucleotides upstream from the canonical GT splice donor site in intron 7. Multiple splice prediction models predict that this substitution creates a cryptic splice donor site that is stronger than the natural donor site. Use of the cryptic splice site is expected to lead to abnormal gene splicing which would be expected to create an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Therefore, c.824 C>T is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MGA-MITOP panel(s).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000802707.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant has been reported in an infant with an inborn error of metabolism (PMID 32778825).  However, no functional data supporting the pathogenicity of this variant was provided.    This variant has been reported in ClinVar (Variation ID: 214149). The overall minor allele frequency for this variant (rs748318386) is approximately 0.0041%. An in silico tool predicts that this variant may impact RNA splicing. Taken together, evidence is not sufficient to determine whether this variant is benign or pathogenic. Therefore, this variant is classified as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024