rs773515

chr9-91220650-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001698.3(AUH):c.843+155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,136 control chromosomes in the GnomAD database, including 22,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (22153 hom., cov: 33)
• Consequence: AUH NM_001698.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.317

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-91220650-C-T is Benign according to our data. Variant chr9-91220650-C-T is described in ClinVar as [Benign]. Clinvar id is 683368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUH	NM_001698.3	c.843+155G>A		intron_variant		ENST00000375731.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUH	ENST00000375731.9	c.843+155G>A		intron_variant		1	NM_001698.3	P1
AUH	ENST00000303617.5	c.756+155G>A		intron_variant		1
AUH	ENST00000473695.1	n.115+155G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77474 AN: 152018 Hom.: 22155 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.509 AC: 77490 AN: 152136 Hom.: 22153 Cov.: 33 AF XY: 0.507 AC XY: 37739 AN XY: 74368

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.535

Alfa AF: 0.613 Hom.: 28380

Bravo AF: 0.497

Asia WGS AF: 0.410 AC: 1424 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.3
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs773515; hg19: chr9-93982932;