12-81143874-C-T

Variant names:

• chr12-81143874-C-T
• rs769056
• NM_024560.4:c.921+627C>T

Variant summary

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

The NM_024560.4(ACSS3):​c.921+627C>T 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 152,174 control chromosomes in the GnomAD database, including 58,998 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 (58998 hom., cov: 33)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 2 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=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	NM_024560.4	MANE Select	c.921+627C>T		intron	N/A	NP_078836.1
	ACSS3	NM_001330242.2		c.918+627C>T		intron	N/A	NP_001317171.1
	ACSS3	NM_001330243.2		c.-85+627C>T		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.921+627C>T		intron	N/A	ENSP00000449535.1
	ACSS3	ENST00000261206.7	TSL:1	c.918+627C>T		intron	N/A	ENSP00000261206.3

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132164 AN: 152056 Hom.: 58975 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.869 AC: 132241 AN: 152174 Hom.: 58998 Cov.: 33 AF XY: 0.870 AC XY: 64737 AN XY: 74398

African (AFR) AF: 0.653 AC: 27089 AN: 41466

American (AMR) AF: 0.948 AC: 14490 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3394 AN: 3472

East Asian (EAS) AF: 0.738 AC: 3809 AN: 5160

South Asian (SAS) AF: 0.856 AC: 4136 AN: 4830

European-Finnish (FIN) AF: 0.963 AC: 10213 AN: 10608

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

European-Non Finnish (NFE) AF: 0.970 AC: 66019 AN: 68028

Other (OTH) AF: 0.909 AC: 1919 AN: 2112

Alfa AF: 0.938 Hom.: 31802

Bravo AF: 0.857

Asia WGS AF: 0.810 AC: 2810 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.53
PhyloP100		0.23
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: rs769056; hg19: chr12-81537653;