Variant NM_001098.3:c.192A>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098.3(ACO2):c.192A>C(p.Thr64Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,613,368 control chromosomes in the GnomAD database, including 58,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7797 hom., cov: 32)

Exomes 𝑓: 0.24 ( 51036 hom. )

Consequence

ACO2
NM_001098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.883

Variant links:

Genes affected

ACO2 (HGNC:118): (aconitase 2) The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

ACO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 22-41507809-A-C is Benign according to our data. Variant chr22-41507809-A-C is described in ClinVar as [Benign]. Clinvar id is 128256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41507809-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACO2	NM_001098.3 link	c.192A>C	p.Thr64Thr	synonymous_variant	Exon 3 of 18	ENST00000216254.9	NP_001089.1	Q99798

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACO2	ENST00000216254.9 link	c.192A>C	p.Thr64Thr	synonymous_variant	Exon 3 of 18	1	NM_001098.3	ENSP00000216254.4		Q99798

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45179

AN:

151834

Hom.:

7779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.334

AC:

83458

AN:

249530

Hom.:

17715

AF XY:

0.323

AC XY:

43582

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.244

AC:

356759

AN:

1461416

Hom.:

51036

Cov.:

AF XY:

0.246

AC XY:

179127

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.368

Gnomad4 AMR exome

AF:

0.626

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.298

AC:

45241

AN:

151952

Hom.:

7797

Cov.:

AF XY:

0.308

AC XY:

22837

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.403

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.233

Hom.:

6664

Bravo

AF:

0.321

Asia WGS

AF:

0.398

AC:

1380

AN:

3472

EpiCase

AF:

0.224

EpiControl

AF:

0.215

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Oct 24, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Optic atrophy 9

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Infantile cerebellar-retinal degeneration

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.8

DANN

Benign

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over