Variant 3-38129319-C-G 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_001607.4(ACAA1):c.516G>C(p.Glu172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,526 control chromosomes in the GnomAD database, including 18,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1645 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17285 hom. )

Consequence

ACAA1
NM_001607.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.285

Variant links:

Genes affected

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACAA1 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=0.0011505485).

BP6

Variant 3-38129319-C-G is Benign according to our data. Variant chr3-38129319-C-G is described in ClinVar as [Benign]. Clinvar id is 1277354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAA1	NM_001607.4 link	c.516G>C	p.Glu172Asp	missense_variant	6/12	ENST00000333167.13	NP_001598.1	P09110-1A0A024R2M6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAA1	ENST00000333167.13 link	c.516G>C	p.Glu172Asp	missense_variant	6/12	1	NM_001607.4	ENSP00000333664.8		P09110-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19632

AN:

152104

Hom.:

1647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.0920

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.157

AC:

39481

AN:

251324

Hom.:

3775

AF XY:

0.151

AC XY:

20545

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0429

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.360

Gnomad SAS exome

AF:

0.0798

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.146

AC:

212807

AN:

1461304

Hom.:

17285

Cov.:

AF XY:

0.144

AC XY:

104463

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.0378

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.0812

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.129

AC:

19630

AN:

152222

Hom.:

1645

Cov.:

AF XY:

0.131

AC XY:

9772

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0420

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.0925

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.136

Hom.:

1198

Bravo

AF:

0.124

TwinsUK

AF:

0.145

AC:

537

ALSPAC

AF:

0.155

AC:

596

ESP6500AA

AF:

0.0468

AC:

206

ESP6500EA

AF:

0.145

AC:

1251

ExAC

AF:

0.153

AC:

18563

Asia WGS

AF:

0.171

AC:

594

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.136

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 22151743) -

ACAA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.26

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.21

Sift

Benign

0.25

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;B

Vest4

0.060

MutPred

0.15

Loss of sheet (P = 0.0817);.;

MPC

0.31

ClinPred

0.0035

GERP RS

1.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.13

gMVP

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

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