12-81081854-G-A

Position:

• chr12-81081854-G-A

Variant summary

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

The NM_024560.4(ACSS3):​c.311+3423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,144 control chromosomes in the GnomAD database, including 52,936 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 0.83 (52936 hom., cov: 32)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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 (AMR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.311+3423G>A		intron_variant		ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.311+3423G>A		intron_variant		1	NM_024560.4	ENSP00000449535	A1
ACSS3	ENST00000261206.7	c.308+3426G>A		intron_variant		1		ENSP00000261206	P4
ACSS3	ENST00000549175.1	c.-13-27706G>A		intron_variant		5		ENSP00000447748

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126171 AN: 152028 Hom.: 52908 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.830 AC: 126249 AN: 152144 Hom.: 52936 Cov.: 32 AF XY: 0.829 AC XY: 61651 AN XY: 74376

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.841

Alfa AF: 0.883 Hom.: 87187

Bravo AF: 0.826

Asia WGS AF: 0.804 AC: 2797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.19

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: rs7138951; hg19: chr12-81475633;