rs769056

Positions:

• chr12-81143874-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS3	NM_024560.4	c.921+627C>T		intron_variant		ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6	c.921+627C>T		intron_variant		1	NM_024560.4	A1
ACSS3	ENST00000261206.7	c.918+627C>T		intron_variant		1		P4

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

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.909

Alfa AF: 0.938 Hom.: 28056

Bravo AF: 0.857

Asia WGS AF: 0.810 AC: 2810 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.53

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: rs769056; hg19: chr12-81537653;