rs1468611034

Variant names:

• chr6-159776234-C-G
• rs1468611034
• NM_005891.3:c.719C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-159776234-C-G
• chr6-159776234-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005891.3(ACAT2):​c.719C>G​(p.Thr240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ACAT2 NM_005891.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22361332).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005891.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT2	NM_005891.3	MANE Select	c.719C>G	p.Thr240Ser	missense	Exon 6 of 9	NP_005882.2	Q9BWD1-1
	ACAT2	NM_001303253.1		c.806C>G	p.Thr269Ser	missense	Exon 6 of 9	NP_001290182.1	Q9BWD1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT2	ENST00000367048.5	TSL:1 MANE Select	c.719C>G	p.Thr240Ser	missense	Exon 6 of 9	ENSP00000356015.4	Q9BWD1-1
	ACAT2	ENST00000869581.1		c.746C>G	p.Thr249Ser	missense	Exon 6 of 9	ENSP00000539640.1
	ACAT2	ENST00000869587.1		c.743C>G	p.Thr248Ser	missense	Exon 6 of 9	ENSP00000539646.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.23
Sift	Benign	0.034	D
Sift4G	Uncertain	0.039	D
Polyphen		0.0	B
Vest4		0.20
MVP		0.88
MPC		0.11
ClinPred		0.49	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.53
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1468611034; hg19: chr6-160197266;