rs1435964

Positions:

• chr12-81148436-T-C

Variant summary

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

The ENST00000548058.6(ACSS3):​c.922-3408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,102 control chromosomes in the GnomAD database, including 10,239 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 0.35 (10239 hom., cov: 31)
• Consequence: ACSS3 ENST00000548058.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.922-3408T>C		intron_variant		ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.922-3408T>C		intron_variant		1	NM_024560.4	ENSP00000449535	A1
ACSS3	ENST00000261206.7	c.919-3408T>C		intron_variant		1		ENSP00000261206	P4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53649 AN: 151984 Hom.: 10234 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.353 AC: 53654 AN: 152102 Hom.: 10239 Cov.: 31 AF XY: 0.347 AC XY: 25842 AN XY: 74376

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.378

Alfa AF: 0.391 Hom.: 5088

Bravo AF: 0.351

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1435964; hg19: chr12-81542215;