11-108121611-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001386685.1(ACAT1):c.-360C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,550,728 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 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ACAT1
NM_001386685.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.850

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

beta-ketothiolase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACAT1 links:

ENSG00000255467 (HGNC:):

ENSG00000255467 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31211615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386685.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAT1	NM_000019.4	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 12	NP_000010.1	P24752-1
ACAT1	NM_001386685.1		c.-360C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001373614.1	A0A5F9ZHJ0
ACAT1	NM_001386686.1		c.-365C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001373615.1	A0A5F9ZHJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAT1	ENST00000265838.9	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 12	ENSP00000265838.4	P24752-1
ACAT1	ENST00000299355.10	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000299355.6	P24752-2
ACAT1	ENST00000531813.5	TSL:1	n.5C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000435965.1	E9PRQ6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000663

AC:

AN:

150858

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1398476

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31652

American (AMR)

AF:

0.00

AC:

AN:

35808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

35852

South Asian (SAS)

AF:

0.00

AC:

AN:

79274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48062

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

1079290

Other (OTH)

AF:

0.00

AC:

AN:

57970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000565

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of acetyl-CoA acetyltransferase (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.0056

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.0

PhyloP100

0.85

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.23

REVEL

Benign

0.13

Sift

Uncertain

0.017

Sift4G

Uncertain

0.017

Polyphen

0.0010

Vest4

0.23

MutPred

0.38

Gain of sheet (P = 0.0266)

MVP

0.81

MPC

0.18

ClinPred

0.11

GERP RS

1.5

PromoterAI

-0.19

Neutral

(source)

Varity_R

0.11

gMVP

0.67

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over