12-81137000-A-G

Position:

• chr12-81137000-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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.645+1996A>G		intron_variant		ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6	c.645+1996A>G		intron_variant		1	NM_024560.4	A1
ACSS3	ENST00000261206.7	c.642+1996A>G		intron_variant		1		P4
ACSS3	ENST00000548387.1	n.210+1996A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.910

Alfa AF: 0.960 Hom.: 127244

Bravo AF: 0.857

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.58

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: rs2574730; hg19: chr12-81530779;