12-81100473-T-G

Variant names:

• chr12-81100473-T-G
• rs12296937
• NM_024560.4:c.312-9087T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024560.4(ACSS3):​c.312-9087T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 152,236 control chromosomes in the GnomAD database, including 304 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 0.051 (304 hom., cov: 31)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 5 publications found

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]

ENSG00000258026 (HGNC:58286):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	NM_024560.4	MANE Select	c.312-9087T>G		intron	N/A	NP_078836.1
	ACSS3	NM_001330242.2		c.309-9087T>G		intron	N/A	NP_001317171.1
	ACSS3	NM_001330243.2		c.-694-9087T>G		intron	N/A	NP_001317172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.312-9087T>G		intron	N/A	ENSP00000449535.1
	ACSS3	ENST00000261206.7	TSL:1	c.309-9087T>G		intron	N/A	ENSP00000261206.3
	ACSS3	ENST00000549175.1	TSL:5	c.-13-9087T>G		intron	N/A	ENSP00000447748.1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7696 AN: 152118 Hom.: 299 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0507 AC: 7724 AN: 152236 Hom.: 304 Cov.: 31 AF XY: 0.0508 AC XY: 3780 AN XY: 74442

African (AFR) AF: 0.105 AC: 4371 AN: 41512

American (AMR) AF: 0.0192 AC: 293 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.0524 AC: 271 AN: 5170

South Asian (SAS) AF: 0.104 AC: 500 AN: 4822

European-Finnish (FIN) AF: 0.0263 AC: 279 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0274 AC: 1864 AN: 68028

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0380 Hom.: 91

Bravo AF: 0.0507

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.57
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12296937; hg19: chr12-81494252;