rs10492002

chr12-81150757-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.922-1087C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,124 control chromosomes in the GnomAD database, including 8,784 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 0.30 (8784 hom., cov: 33)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS3	NM_024560.4	c.922-1087C>T		intron_variant		ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6	c.922-1087C>T		intron_variant		1	NM_024560.4	A1
ACSS3	ENST00000261206.7	c.919-1087C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46161 AN: 152006 Hom.: 8783 Cov.: 33

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.303 AC: 46154 AN: 152124 Hom.: 8784 Cov.: 33 AF XY: 0.300 AC XY: 22322 AN XY: 74388

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.345

Alfa AF: 0.389 Hom.: 6361

Bravo AF: 0.295

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.047
Dann	Benign	0.64

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: rs10492002; hg19: chr12-81544536;