chr9-91220210-G-A

Variant names:

• chr9-91220210-G-A
• rs9785225
• NM_001698.3:c.843+595C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001698.3(AUH):​c.843+595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,194 control chromosomes in the GnomAD database, including 1,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1127 hom., cov: 33)
• Consequence: AUH NM_001698.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUH	NM_001698.3	c.843+595C>T		intron_variant	Intron 7 of 9	ENST00000375731.9	NP_001689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUH	ENST00000375731.9	c.843+595C>T		intron_variant	Intron 7 of 9	1	NM_001698.3	ENSP00000364883.5
AUH	ENST00000303617.5	c.756+595C>T		intron_variant	Intron 6 of 8	1		ENSP00000307334.5
AUH	ENST00000473695.1	n.115+595C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17368 AN: 152076 Hom.: 1121 Cov.: 33

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17386 AN: 152194 Hom.: 1127 Cov.: 33 AF XY: 0.115 AC XY: 8555 AN XY: 74410

African (AFR) AF: 0.0959 AC: 3982 AN: 41536

American (AMR) AF: 0.118 AC: 1808 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1645 AN: 5158

South Asian (SAS) AF: 0.137 AC: 661 AN: 4824

European-Finnish (FIN) AF: 0.0925 AC: 980 AN: 10596

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7441 AN: 68010

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.115 Hom.: 3462

Bravo AF: 0.119

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.49
PhyloP100		-1.1
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: rs9785225; hg19: chr9-93982492;