Variant chr6-159767007-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005891.3(ACAT2):c.193T>G(p.Cys65Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACAT2
NM_005891.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34393263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAT2	NM_005891.3 linkuse as main transcript	c.193T>G	p.Cys65Gly	missense_variant, splice_region_variant	3/9	ENST00000367048.5
ACAT2	NM_001303253.1 linkuse as main transcript	c.280T>G	p.Cys94Gly	missense_variant, splice_region_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAT2	ENST00000367048.5 linkuse as main transcript	c.193T>G	p.Cys65Gly	missense_variant, splice_region_variant	3/9	1	NM_005891.3	P1	Q9BWD1-1
ACAT2	ENST00000467951.1 linkuse as main transcript	n.421T>G		splice_region_variant, non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.193T>G (p.C65G) alteration is located in exon 3 (coding exon 3) of the ACAT2 gene. This alteration results from a T to G substitution at nucleotide position 193, causing the cysteine (C) at amino acid position 65 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.18

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0081

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.074

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.095

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.13

REVEL

Uncertain

0.37

Sift

Benign

0.27

Sift4G

Benign

0.38

Polyphen

0.070

Vest4

0.44

MVP

0.94

MPC

0.24

ClinPred

0.30

GERP RS

5.7

Varity_R

0.34

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over