chr9-91214288-C-T

Variant names:

• chr9-91214288-C-T
• rs1564001076
• NM_001698.3:c.*60G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001698.3(AUH):​c.*60G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,288,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: AUH NM_001698.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.570
• Publications: 0 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

ENSG00000306114 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.*60G>A		3_prime_UTR	Exon 10 of 10	NP_001689.1	Q13825-1
	AUH	NM_001306190.2		c.*60G>A		3_prime_UTR	Exon 9 of 9	NP_001293119.1	Q13825-2
	AUH	NM_001351431.2		c.*60G>A		3_prime_UTR	Exon 11 of 11	NP_001338360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUH	ENST00000375731.9	TSL:1 MANE Select	c.*60G>A		3_prime_UTR	Exon 10 of 10	ENSP00000364883.5	Q13825-1
	AUH	ENST00000303617.5	TSL:1	c.*60G>A		3_prime_UTR	Exon 9 of 9	ENSP00000307334.5	Q13825-2
	AUH	ENST00000895926.1		c.*60G>A		3_prime_UTR	Exon 11 of 11	ENSP00000565985.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000776 AC: 10 AN: 1288788 Hom.: 0 Cov.: 19 AF XY: 0.00000932 AC XY: 6 AN XY: 644094

African (AFR) AF: 0.00 AC: 0 AN: 29508

American (AMR) AF: 0.00 AC: 0 AN: 39216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24576

East Asian (EAS) AF: 0.00 AC: 0 AN: 36888

South Asian (SAS) AF: 0.0000380 AC: 3 AN: 78864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00000617 AC: 6 AN: 972510

Other (OTH) AF: 0.0000184 AC: 1 AN: 54250

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	3-methylglutaconic aciduria type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		-0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1564001076; hg19: chr9-93976570; COSMIC: COSV57864869; COSMIC: COSV57864869;