12-80943679-T-C

Position:

• chr12-80943679-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549175.1(ACSS3):​c.-151+5761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,072 control chromosomes in the GnomAD database, including 33,771 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 0.63 (33771 hom., cov: 32)
• Consequence: ACSS3 ENST00000549175.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.80943679T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000549175.1	c.-151+5761T>C		intron_variant		5		ENSP00000447748.1
ACSS3	ENST00000650935.1	n.61-5586T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95810 AN: 151956 Hom.: 33773 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.630 AC: 95841 AN: 152072 Hom.: 33771 Cov.: 32 AF XY: 0.631 AC XY: 46945 AN XY: 74344

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.690

Alfa AF: 0.769 Hom.: 58289

Bravo AF: 0.607

Asia WGS AF: 0.670 AC: 2326 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1163656; hg19: chr12-81337458;