12-81127171-A-G

Variant names:

• chr12-81127171-A-G
• rs2701787
• NM_024560.4:c.457-7645A>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.457-7645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 151,750 control chromosomes in the GnomAD database, including 61,139 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 0.89 (61139 hom., cov: 32)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	NM_024560.4	MANE Select	c.457-7645A>G		intron	N/A	NP_078836.1
	ACSS3	NM_001330242.2		c.454-7645A>G		intron	N/A	NP_001317171.1
	ACSS3	NM_001330243.2		c.-549-7645A>G		intron	N/A	NP_001317172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.457-7645A>G		intron	N/A	ENSP00000449535.1
	ACSS3	ENST00000261206.7	TSL:1	c.454-7645A>G		intron	N/A	ENSP00000261206.3
	ACSS3	ENST00000549175.1	TSL:5	c.133-7645A>G		intron	N/A	ENSP00000447748.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135027 AN: 151622 Hom.: 61108 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.976

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.890 AC: 135117 AN: 151750 Hom.: 61139 Cov.: 32 AF XY: 0.891 AC XY: 66074 AN XY: 74162

African (AFR) AF: 0.726 AC: 30112 AN: 41476

American (AMR) AF: 0.958 AC: 14628 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3396 AN: 3472

East Asian (EAS) AF: 0.741 AC: 3814 AN: 5148

South Asian (SAS) AF: 0.856 AC: 4102 AN: 4790

European-Finnish (FIN) AF: 0.964 AC: 10198 AN: 10584

Middle Eastern (MID) AF: 0.975 AC: 197 AN: 202

European-Non Finnish (NFE) AF: 0.971 AC: 65841 AN: 67810

Other (OTH) AF: 0.928 AC: 1942 AN: 2092

Alfa AF: 0.916 Hom.: 8356

Bravo AF: 0.883

Asia WGS AF: 0.812 AC: 2760 AN: 3398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.098
DANN	Benign	0.69
PhyloP100		-0.88
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: rs2701787; hg19: chr12-81520950;