17-37089042-C-A

Variant names:

• chr17-37089042-C-A
• rs141608509
• NM_198834.3:c.6924G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_198834.3(ACACA):​c.6924G>T​(p.Ala2308Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A2308A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACACA NM_198834.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 0 publications found

Genes affected

ACACA (HGNC:84): (acetyl-CoA carboxylase alpha) 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. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACACA Gene-Disease associations (from GenCC):

• acetyl-coa carboxylase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP7: Synonymous conserved (PhyloP=0.149 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198834.3. 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
	ACACA	NM_198834.3	MANE Select	c.6924G>T	p.Ala2308Ala	synonymous	Exon 55 of 56	NP_942131.1	Q13085-4
	ACACA	NM_198836.3		c.6813G>T	p.Ala2271Ala	synonymous	Exon 55 of 56	NP_942133.1	Q13085-1
	ACACA	NM_198839.3		c.6813G>T	p.Ala2271Ala	synonymous	Exon 59 of 60	NP_942136.1	Q13085-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	ENST00000616317.5	TSL:1 MANE Select	c.6924G>T	p.Ala2308Ala	synonymous	Exon 55 of 56	ENSP00000483300.1	Q13085-4
	ACACA	ENST00000614428.4	TSL:1	c.6813G>T	p.Ala2271Ala	synonymous	Exon 55 of 56	ENSP00000478547.1	Q13085-1
	ACACA	ENST00000619546.4	TSL:1	c.2769G>T	p.Ala923Ala	synonymous	Exon 22 of 23	ENSP00000483969.1	Q59FY4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251470 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	4.0
DANN	Benign	0.77
PhyloP100		0.15
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141608509; hg19: chr17-35445977;