ENST00000549175.1:c.-14+21050G>C

Variant names:

• chr12-81043569-G-C
• rs10506838
• ENST00000549175.1:c.-14+21050G>C

Variant summary

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

The ENST00000549175.1(ACSS3):​c.-14+21050G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,042 control chromosomes in the GnomAD database, including 652 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 0.080 (652 hom., cov: 32)
• Consequence: ACSS3 ENST00000549175.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815

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 (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000549175.1	c.-14+21050G>C		intron_variant	Intron 2 of 3	5		ENSP00000447748.1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12089 AN: 151924 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0796 AC: 12099 AN: 152042 Hom.: 652 Cov.: 32 AF XY: 0.0824 AC XY: 6122 AN XY: 74290

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0599 Hom.: 51

Bravo AF: 0.0797

Asia WGS AF: 0.172 AC: 599 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10506838; hg19: chr12-81437348;