NM_001698.3(AUH):c.824C>T (p.Ala275Val) AND 3-methylglutaconic aciduria type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 24, 2023
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:: RCV001853168.6

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)

Name:: 3-methylglutaconic aciduria type 1
Synonyms:: 3 methylglutaconic aciduria type I; MGA type I; 3 alpha methylglutaconic aciduria type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009610; MedGen: C0342727; Orphanet: 67046; OMIM: 250950

Recent activity

Clear Turn Off Turn On

At.1154 AND (alive[prop]) (1)
Gene
SAC9 sacI homology domain-containing protein / WW domain-containing protein [Ara...
SAC9 sacI homology domain-containing protein / WW domain-containing protein [Arabidopsis thaliana]
Gene ID:825146

Gene
RecName: Full=DET1- and DDB1-associated protein 1; AltName: Full=Placenta cross-...
RecName: Full=DET1- and DDB1-associated protein 1; AltName: Full=Placenta cross-immune reaction antigen 1; Short=PCIA-1
gi|74733400|sp|Q9BW61.1|DDA1_HUMAN

Protein
Leukoencephalopathy with vanishing white matter 3
Leukoencephalopathy with vanishing white matter 3

MedGen

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
SCV002205214	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 24, 2023)	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

SCV002205214

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 24, 2023)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002205214.3

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

Description

This missense change has been observed in individual(s) with clinical features of 3-methylglutaconic aciduria (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AUH protein function. ClinVar contains an entry for this variant (Variation ID: 214149). This variant is present in population databases (rs748318386, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 275 of the AUH protein (p.Ala275Val).

#	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