12-81137000-A-G

Variant names:

• chr12-81137000-A-G
• rs2574730
• NM_024560.4:c.645+1996A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024560.4(ACSS3):​c.645+1996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,034 control chromosomes in the GnomAD database, including 58,962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58962 hom., cov: 30)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 3 publications found

Genes affected

ACSS3 (HGNC:24723): (acyl-CoA synthetase short chain family member 3) Enables propionate-CoA ligase activity. Predicted to be involved in ketone body biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024560.4. 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
	ACSS3	NM_024560.4	MANE Select	c.645+1996A>G		intron	N/A	NP_078836.1	Q9H6R3-1
	ACSS3	NM_001330242.2		c.642+1996A>G		intron	N/A	NP_001317171.1	A0A0B4J1R2
	ACSS3	NM_001330243.2		c.-361+1996A>G		intron	N/A	NP_001317172.1	Q9H6R3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.645+1996A>G		intron	N/A	ENSP00000449535.1	Q9H6R3-1
	ACSS3	ENST00000261206.7	TSL:1	c.642+1996A>G		intron	N/A	ENSP00000261206.3	A0A0B4J1R2
	ACSS3	ENST00000965760.1		c.645+1996A>G		intron	N/A	ENSP00000635819.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132064 AN: 151916 Hom.: 58940 Cov.: 30

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.869 AC: 132141 AN: 152034 Hom.: 58962 Cov.: 30 AF XY: 0.870 AC XY: 64682 AN XY: 74322

African (AFR) AF: 0.653 AC: 27012 AN: 41372

American (AMR) AF: 0.948 AC: 14485 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3392 AN: 3470

East Asian (EAS) AF: 0.739 AC: 3815 AN: 5160

South Asian (SAS) AF: 0.857 AC: 4129 AN: 4820

European-Finnish (FIN) AF: 0.963 AC: 10209 AN: 10604

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66006 AN: 68010

Other (OTH) AF: 0.910 AC: 1921 AN: 2110

Alfa AF: 0.952 Hom.: 189690

Bravo AF: 0.857

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs2574730; hg19: chr12-81530779;