Variant 13-76953608-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001258406.2(ACOD1):c.183T>G(p.Ser61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,544,678 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

ACOD1
NM_001258406.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.221

Variant links:

Genes affected

ACOD1 (HGNC:33904): (aconitate decarboxylase 1) Enables aconitate decarboxylase activity. Involved in defense response; positive regulation of antimicrobial humoral response; and tolerance induction to lipopolysaccharide. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACOD1 links:

LOC105370269 (HGNC:):

LOC105370269 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006529242).

BP6

Variant 13-76953608-T-G is Benign according to our data. Variant chr13-76953608-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643848.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOD1	NM_001258406.2 linkuse as main transcript	c.183T>G	p.Ser61Arg	missense_variant	3/5	ENST00000377462.6	NP_001245335.1	A6NK06
ACOD1	XM_047430581.1 linkuse as main transcript	c.87T>G	p.Ser29Arg	missense_variant	2/4		XP_047286537.1
LOC105370269	XR_001749929.1 linkuse as main transcript	n.213-10737A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOD1	ENST00000377462.6 linkuse as main transcript	c.183T>G	p.Ser61Arg	missense_variant	3/5	5	NM_001258406.2	ENSP00000366682.1		A6NK06

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00278

AC:

419

AN:

150862

Hom.:

AF XY:

0.00249

AC XY:

201

AN XY:

80880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00737

Gnomad EAS exome

AF:

0.000927

Gnomad SAS exome

AF:

0.000444

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.000410

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00106

AC:

1480

AN:

1392294

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

743

AN XY:

686676

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00648

Gnomad4 EAS exome

AF:

0.000814

Gnomad4 SAS exome

AF:

0.000507

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152384

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.00323

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ACOD1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

0.014

Eigen_PC

Benign

-0.0057

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.016

D;D

Vest4

0.25

MutPred

0.39

Gain of catalytic residue at S66 (P = 4e-04);Gain of catalytic residue at S66 (P = 4e-04);

MVP

0.088

ClinPred

0.045

GERP RS

3.7

Varity_R

0.36

gMVP

0.64

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

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