6-159767158-TT-AC

Variant names:

• chr6-159767158-TT-AC
• NM_005891.3:c.344_345delTTinsAC
• ACAT2 p.Val115Asp

Variant summary

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

The NM_005891.3(ACAT2):​c.344_345delTTinsAC​(p.Val115Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACAT2 NM_005891.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• 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.

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.344_345delTTinsAC	p.Val115Asp	missense	N/A	NP_005882.2	Q9BWD1-1
	ACAT2	NM_001303253.1		c.431_432delTTinsAC	p.Val144Asp	missense	N/A	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.344_345delTTinsAC	p.Val115Asp	missense	N/A	ENSP00000356015.4	Q9BWD1-1
	ACAT2	ENST00000869581.1		c.344_345delTTinsAC	p.Val115Asp	missense	N/A	ENSP00000539640.1
	ACAT2	ENST00000869587.1		c.368_369delTTinsAC	p.Val123Asp	missense	N/A	ENSP00000539646.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-160188190;