rs12985

Variant names:

• chr9-32450189-T-A
• rs12985
• NM_002197.3:c.*78T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-32450189-T-A
• chr9-32450189-T-C

Variant summary

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

The NM_002197.3(ACO1):​c.*78T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACO1 NM_002197.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 21 publications found

Genes affected

ACO1 (HGNC:117): (aconitase 1) The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]

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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACO1	NM_002197.3	c.*78T>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000309951.8	NP_002188.1
ACO1	NM_001278352.2	c.*78T>A		3_prime_UTR_variant	Exon 22 of 22		NP_001265281.1
ACO1	NM_001362840.2	c.*78T>A		3_prime_UTR_variant	Exon 22 of 22		NP_001349769.1
ACO1	XM_047423430.1	c.*78T>A		3_prime_UTR_variant	Exon 21 of 21		XP_047279386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACO1	ENST00000309951.8	c.*78T>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_002197.3	ENSP00000309477.5
ACO1	ENST00000379923.5	c.*78T>A		3_prime_UTR_variant	Exon 22 of 22	5		ENSP00000369255.1
ACO1	ENST00000541043.5	c.*78T>A		3_prime_UTR_variant	Exon 22 of 22	5		ENSP00000438733.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 999304 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 517126

African (AFR) AF: 0.00 AC: 0 AN: 24300

American (AMR) AF: 0.00 AC: 0 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23234

East Asian (EAS) AF: 0.00 AC: 0 AN: 37558

South Asian (SAS) AF: 0.00 AC: 0 AN: 76562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 693938

Other (OTH) AF: 0.00 AC: 0 AN: 44872

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.42
PhyloP100		-0.42

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: rs12985; hg19: chr9-32450187;