9-91325340-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001698.3(AUH):c.483A>C(p.Ile161Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,613,346 control chromosomes in the GnomAD database, including 8,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1128 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7664 hom. )

Consequence

AUH
NM_001698.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.636

Variant links:

Genes affected

AUH (HGNC:890): (AU RNA binding methylglutaconyl-CoA hydratase) This gene encodes bifunctional mitochondrial protein that has both RNA-binding and hydratase activities. The encoded protein is a methylglutaconyl-CoA hydratase that catalyzes the hydration of 3-methylglutaconyl-CoA to 3-hydroxy-3-methyl-glutaryl-CoA, a critical step in the leucine degradation pathway. This protein also binds AU-rich elements (AREs) found in the 3' UTRs of rapidly decaying mRNAs including c-fos, c-myc and granulocyte/ macrophage colony stimulating factor. ARE elements are involved in directing RNA to rapid degradation and deadenylation. This protein is localizes to the mitochondrial matrix and the inner mitochondrial membrane and may be involved in mitochondrial protein synthesis. Mutations in this gene are the cause of 3-methylglutaconic aciduria, type I. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

AUH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-91325340-T-G is Benign according to our data. Variant chr9-91325340-T-G is described in ClinVar as [Benign]. Clinvar id is 128520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-91325340-T-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.636 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUH	NM_001698.3 link	c.483A>C	p.Ile161Ile	synonymous_variant	Exon 4 of 10	ENST00000375731.9	NP_001689.1	Q13825-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AUH	ENST00000375731.9 link	c.483A>C	p.Ile161Ile	synonymous_variant	Exon 4 of 10	1	NM_001698.3	ENSP00000364883.5	Q13825-1
AUH	ENST00000303617.5 link	c.419-27264A>C		intron_variant	Intron 3 of 8	1		ENSP00000307334.5	Q13825-2
AUH	ENST00000478465.5 link	n.643A>C		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17393

AN:

152098

Hom.:

1126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0808

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.0505

Gnomad FIN

AF:

0.0792

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0839

AC:

21101

AN:

251374

Hom.:

1129

AF XY:

0.0824

AC XY:

11198

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0138

Gnomad SAS exome

AF:

0.0469

Gnomad FIN exome

AF:

0.0757

Gnomad NFE exome

AF:

0.0996

Gnomad OTH exome

AF:

0.0953

GnomAD4 exome

AF:

0.0984

AC:

143807

AN:

1461130

Hom.:

7664

Cov.:

AF XY:

0.0966

AC XY:

70202

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0550

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0217

Gnomad4 SAS exome

AF:

0.0500

Gnomad4 FIN exome

AF:

0.0751

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.114

AC:

17413

AN:

152216

Hom.:

1128

Cov.:

AF XY:

0.111

AC XY:

8278

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.0807

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.0792

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.100

Hom.:

1912

Bravo

AF:

0.119

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

3-methylglutaconic aciduria type 1

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.7

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over