Variant 18-49792313-A-T 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_006111.3(ACAA2):c.592T>A(p.Tyr198Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,410 control chromosomes in the GnomAD database, including 163 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 0.0015 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 159 hom. )

Consequence

ACAA2
NM_006111.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

ACAA2 (HGNC:83): (acetyl-CoA acyltransferase 2) The encoded protein catalyzes the last step of the mitochondrial fatty acid beta-oxidation spiral. Unlike most mitochondrial matrix proteins, it contains a non-cleavable amino-terminal targeting signal. [provided by RefSeq, Jul 2008]

ACAA2 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=0.011936933).

BP6

Variant 18-49792313-A-T is Benign according to our data. Variant chr18-49792313-A-T is described in ClinVar as [Benign]. Clinvar id is 726897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAA2	NM_006111.3 linkuse as main transcript	c.592T>A	p.Tyr198Asn	missense_variant	6/10	ENST00000285093.15	NP_006102.2	P42765B3KNP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACAA2	ENST00000285093.15 linkuse as main transcript	c.592T>A	p.Tyr198Asn	missense_variant	6/10	1	NM_006111.3	ENSP00000285093.8	P42765
ACAA2	ENST00000587994.5 linkuse as main transcript	c.583T>A	p.Tyr195Asn	missense_variant	6/10	5		ENSP00000466015.1	A0A0B4J2A4
ACAA2	ENST00000589432.5 linkuse as main transcript	c.427T>A	p.Tyr143Asn	missense_variant	6/10	5		ENSP00000466466.1	K7EME0

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00662

AC:

1661

AN:

251072

Hom.:

AF XY:

0.00906

AC XY:

1230

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0534

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00323

AC:

4722

AN:

1461054

Hom.:

159

Cov.:

AF XY:

0.00469

AC XY:

3408

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0515

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152356

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

174

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0466

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00743

AC:

902

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Oct 17, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Uncertain

0.71

D;D;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.7

D;.;.

REVEL

Uncertain

0.41

Sift

Benign

0.28

T;.;.

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.56

MVP

0.96

MPC

0.071

ClinPred

0.036

GERP RS

3.1

Varity_R

0.48

gMVP

0.71

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