NM_001698.3(AUH):c.656G>C (p.Gly219Ala) AND 3-methylglutaconic aciduria type 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 28, 2021
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:: RCV001936279.8

Allele description

NM_001698.3(AUH):c.656G>C (p.Gly219Ala)

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.656G>C (p.Gly219Ala)

HGVS:

NC_000009.12:g.91220992C>G
NG_008017.1:g.145933G>C
NM_001306190.2:c.569G>C
NM_001351431.2:c.329G>C
NM_001351432.2:c.329G>C
NM_001351433.2:c.329G>C
NM_001698.2:c.656G>C
NM_001698.3:c.656G>CMANE SELECT
NP_001293119.1:p.Gly190Ala
NP_001338360.1:p.Gly110Ala
NP_001338361.1:p.Gly110Ala
NP_001338362.1:p.Gly110Ala
NP_001689.1:p.Gly219Ala
LRG_449t1:c.656G>C
LRG_449:g.145933G>C
NC_000009.11:g.93983274C>G

Protein change:

G110A

Links:

dbSNP: rs1827104191

NCBI 1000 Genomes Browser:

rs1827104191

Molecular consequence:

NM_001306190.2:c.569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351431.2:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351432.2:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351433.2:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001698.3:c.656G>C - 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

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
SCV002201676	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003834530	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 28, 2021)	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

SCV002201676

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 2, 2021)

germline

clinical testing

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

SCV003834530

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 28, 2021)

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

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 Invitae, SCV002201676.3

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

Description

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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with AUH-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 219 of the AUH protein (p.Gly219Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine.

#	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, SCV003834530.2

#	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

Last Updated: Mar 16, 2024

ClinVar

Relating variation to medicine