dbSNP rs371307389: ACAT2:p.Glu176Lys (chr6-159775205-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005891.3(ACAT2):c.526G>A(p.Glu176Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000644 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

ACAT2
NM_005891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

Publications

4 publications found

Variant links:

Genes affected

ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACAT2 Gene-Disease associations (from GenCC):

acetyl-CoA acetyltransferase-2 deficiency
Inheritance: AR, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

ACAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26599914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAT2	NM_005891.3 link	c.526G>A	p.Glu176Lys	missense_variant	Exon 5 of 9	ENST00000367048.5	NP_005882.2
ACAT2	NM_001303253.1 link	c.613G>A	p.Glu205Lys	missense_variant	Exon 5 of 9		NP_001290182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ACAT2	ENST00000367048.5 link	c.526G>A	p.Glu176Lys	missense_variant	Exon 5 of 9	1	NM_005891.3	ENSP00000356015.4
ACAT2	ENST00000467951.1 link	n.754G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3
ACAT2	ENST00000472052.1 link	n.-81G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000103

AC:

AN:

251230

AF XY:

0.000125

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.000157

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000209

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1111958

Other (OTH)

AF:

0.000199

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000413

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acetyl-CoA acetyltransferase-2 deficiency

Uncertain:1

Mar 05, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.024

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

PhyloP100

5.3

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.18

Sift

Benign

0.035

Sift4G

Uncertain

0.043

Vest4

0.33

ClinPred

0.12

GERP RS

4.9

Varity_R

0.65

gMVP

0.73

Mutation Taster

=44/56

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over