NM_023928.5:c.352A>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023928.5(AACS):​c.352A>T​(p.Ile118Phe) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050519824).

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>T	p.Ile118Phe	missense	Exon 3 of 18	NP_076417.2
	AACS	NM_001414675.1		c.352A>T	p.Ile118Phe	missense	Exon 3 of 17	NP_001401604.1
	AACS	NM_001319840.2		c.352A>T	p.Ile118Phe	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>T	p.Ile118Phe	missense	Exon 3 of 18	ENSP00000324842.6
	AACS	ENST00000852618.1		c.352A>T	p.Ile118Phe	missense	Exon 3 of 18	ENSP00000522677.1
	AACS	ENST00000852617.1		c.352A>T	p.Ile118Phe	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	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.2
DANN	Benign	0.20
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.6	N
PhyloP100		5.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.56		Loss of methylation at K123 (P = 0.1024)
MVP		0.030
MPC		0.18
ClinPred		0.044	T
GERP RS		3.4
Varity_R		0.037
gMVP		0.54
Mutation Taster		=97/3	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;