rs7874056

Variant names:

• chr9-91325340-T-G
• rs7874056
• NM_001698.3:c.483A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-91325340-T-G
• chr9-91325340-T-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.636
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 128520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001698.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUH	NM_001698.3	MANE Select	c.483A>C	p.Ile161Ile	synonymous	Exon 4 of 10	NP_001689.1	Q13825-1
	AUH	NM_001351431.2		c.156A>C	p.Ile52Ile	synonymous	Exon 5 of 11	NP_001338360.1
	AUH	NM_001351432.2		c.156A>C	p.Ile52Ile	synonymous	Exon 5 of 11	NP_001338361.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUH	ENST00000375731.9	TSL:1 MANE Select	c.483A>C	p.Ile161Ile	synonymous	Exon 4 of 10	ENSP00000364883.5	Q13825-1
	AUH	ENST00000303617.5	TSL:1	c.419-27264A>C		intron	N/A	ENSP00000307334.5	Q13825-2
	AUH	ENST00000895926.1		c.513A>C	p.Ile171Ile	synonymous	Exon 5 of 11	ENSP00000565985.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17393 AN: 152098 Hom.: 1126 Cov.: 32

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

GnomAD2 exomes AF: 0.0839 AC: 21101 AN: 251374 AF XY: 0.0824

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 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.: 31 AF XY: 0.0966 AC XY: 70202 AN XY: 726888

African (AFR) AF: 0.180 AC: 6011 AN: 33466

American (AMR) AF: 0.0550 AC: 2461 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3160 AN: 26116

East Asian (EAS) AF: 0.0217 AC: 860 AN: 39632

South Asian (SAS) AF: 0.0500 AC: 4310 AN: 86246

European-Finnish (FIN) AF: 0.0751 AC: 4009 AN: 53394

Middle Eastern (MID) AF: 0.0864 AC: 498 AN: 5762

European-Non Finnish (NFE) AF: 0.105 AC: 116328 AN: 1111426

Other (OTH) AF: 0.102 AC: 6170 AN: 60366

GnomAD4 genome AF: 0.114 AC: 17413 AN: 152216 Hom.: 1128 Cov.: 32 AF XY: 0.111 AC XY: 8278 AN XY: 74444

African (AFR) AF: 0.174 AC: 7217 AN: 41516

American (AMR) AF: 0.0807 AC: 1233 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5182

South Asian (SAS) AF: 0.0506 AC: 244 AN: 4824

European-Finnish (FIN) AF: 0.0792 AC: 840 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6991 AN: 68014

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.104 Hom.: 3901

Bravo AF: 0.119

Asia WGS AF: 0.0450 AC: 158 AN: 3478

EpiCase AF: 0.104

EpiControl AF: 0.101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	3-methylglutaconic aciduria type 1 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.7
DANN	Benign	0.78
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7874056; hg19: chr9-94087622; COSMIC: COSV57863314;