12-109139665-G-C

Variant names:

• chr12-109139665-G-C
• rs769981426
• NM_001093.4:c.260G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001093.4(ACACB):​c.260G>C​(p.Arg87Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACACB NM_001093.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

Genes affected

ACACB (HGNC:85): (acetyl-CoA carboxylase beta) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. [provided by RefSeq, Oct 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099877805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.260G>C	p.Arg87Pro	missense_variant	Exon 2 of 53	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.260G>C	p.Arg87Pro	missense_variant	Exon 2 of 53	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.260G>C	p.Arg87Pro	missense_variant	Exon 1 of 52	1		ENSP00000367079.3
ACACB	ENST00000539864.1	c.185G>C	p.Arg62Pro	missense_variant	Exon 2 of 2	3		ENSP00000443494.1
ACACB	ENST00000377854	c.-3743G>C		5_prime_UTR_variant	Exon 1 of 47	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.053
DANN	Benign	0.86
DEOGEN2	Benign	0.38	T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.12	T;D;T
Polyphen		0.0	B;.;B
Vest4		0.12
MutPred		0.34		Loss of MoRF binding (P = 5e-04);.;Loss of MoRF binding (P = 5e-04);
MVP		0.030
MPC		0.34
ClinPred		0.39	T
GERP RS		-7.6
Varity_R		0.073
gMVP		0.086

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

LitVar

Other links and lift over

dbSNP: rs769981426; hg19: chr12-109577470;