Variant 11-108121608-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate

The ENST00000265838.9(ACAT1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ACAT1
ENST00000265838.9 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.55

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 Pathogenic. Variant got 14 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PS1

Another start lost variant in ENST00000265838.9 (ACAT1) was described as [Pathogenic] in ClinVar as 666461

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-108121608-T-A is Pathogenic according to our data. Variant chr11-108121608-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 2838.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAT1	NM_000019.4 linkuse as main transcript	c.2T>A	p.Met1?	start_lost	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.2T>A	p.Met1?	start_lost	1/12	1	NM_000019.4	ENSP00000265838	P1	P24752-1
	ENST00000525548.1 linkuse as main transcript	n.77A>T		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1398374

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689860

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of acetyl-CoA acetyltransferase

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 1993	- -
Pathogenic, criteria provided, single submitter	research	Department of Pediatrics, Gifu University	May 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Uncertain

0.41

MutationTaster

Benign

1.0

A;A

PROVEAN

Benign

-0.27

N;N

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.076

B;.

Vest4

0.76

MutPred

1.0

Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);

MVP

0.95

ClinPred

0.80

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.84

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