11-108121619-G-C

Position:

chr11-108121619-G-C

Variant summary

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

The NM_000019.4(ACAT1):c.13G>C(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,550,150 control chromosomes in the GnomAD database, including 84,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7292 hom., cov: 34)

Exomes 𝑓: 0.33 ( 76906 hom. )

Consequence

ACAT1
NM_000019.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.168

Variant links:

Genes affected

ACAT1 (HGNC:93): (acetyl-CoA acetyltransferase 1) This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone. [provided by RefSeq, Feb 2009]

ACAT1 links:

(HGNC:):

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 (MetaRNN=8.325577E-4).

BP6

Variant 11-108121619-G-C is Benign according to our data. Variant chr11-108121619-G-C is described in ClinVar as [Benign]. Clinvar id is 92295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108121619-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAT1	NM_000019.4 linkuse as main transcript	c.13G>C	p.Ala5Pro	missense_variant	1/12	ENST00000265838.9	NP_000010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAT1	ENST00000265838.9 linkuse as main transcript	c.13G>C	p.Ala5Pro	missense_variant	1/12	1	NM_000019.4	ENSP00000265838	P1	P24752-1
	ENST00000525548.1 linkuse as main transcript	n.66C>G		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44163

AN:

152138

Hom.:

7292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.366

AC:

55070

AN:

150668

Hom.:

10694

AF XY:

0.371

AC XY:

29973

AN XY:

80832

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.479

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.326

AC:

455226

AN:

1397894

Hom.:

76906

Cov.:

AF XY:

0.331

AC XY:

228601

AN XY:

689712

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.290

AC:

44168

AN:

152256

Hom.:

7292

Cov.:

AF XY:

0.298

AC XY:

22153

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.320

Hom.:

2606

Bravo

AF:

0.289

TwinsUK

AF:

0.317

AC:

1174

ALSPAC

AF:

0.318

AC:

1224

ESP6500AA

AF:

0.122

AC:

498

ESP6500EA

AF:

0.254

AC:

2021

ExAC

AF:

0.198

AC:

17379

Asia WGS

AF:

0.443

AC:

1537

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of acetyl-CoA acetyltransferase

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 05, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.00083

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.015

D;T

Sift4G

Benign

0.37

T;T

Polyphen

0.61

P;.

Vest4

0.22

MPC

0.25

ClinPred

0.0074

GERP RS

0.20

Varity_R

0.14

gMVP

0.75

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