chr12-125076605-A-C

Variant names:

• chr12-125076605-A-C
• rs11549081
• NM_023928.5:c.352A>C

Variant summary

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

The NM_023928.5(AACS):​c.352A>C​(p.Ile118Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AACS NM_023928.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

Genes affected

AACS (HGNC:21298): (acetoacetyl-CoA synthetase) Predicted to enable acetoacetate-CoA ligase activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370052 (HGNC:):

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=0.079848856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023928.5. 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
	AACS	NM_023928.5	MANE Select	c.352A>C	p.Ile118Leu	missense	Exon 3 of 18	NP_076417.2
	AACS	NM_001414675.1		c.352A>C	p.Ile118Leu	missense	Exon 3 of 17	NP_001401604.1
	AACS	NM_001319840.2		c.352A>C	p.Ile118Leu	missense	Exon 3 of 17	NP_001306769.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AACS	ENST00000316519.11	TSL:1 MANE Select	c.352A>C	p.Ile118Leu	missense	Exon 3 of 18	ENSP00000324842.6
	AACS	ENST00000852618.1		c.352A>C	p.Ile118Leu	missense	Exon 3 of 18	ENSP00000522677.1
	AACS	ENST00000852617.1		c.352A>C	p.Ile118Leu	missense	Exon 3 of 18	ENSP00000522676.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.6
DANN	Benign	0.47
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		5.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.16
Sift	Benign	0.68	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.41		Loss of methylation at K123 (P = 0.0508)
MVP		0.12
MPC		0.11
ClinPred		0.056	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.48
Mutation Taster		=96/4	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: rs11549081; hg19: chr12-125561151;