12-81127605-A-T

Position:

• chr12-81127605-A-T

Variant summary

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

The ENST00000548058.6(ACSS3):​c.457-7211A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,210 control chromosomes in the GnomAD database, including 61,116 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 0.89 (61116 hom., cov: 33)
• Consequence: ACSS3 ENST00000548058.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.457-7211A>T		intron_variant		ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.457-7211A>T		intron_variant		1	NM_024560.4	ENSP00000449535	A1
ACSS3	ENST00000261206.7	c.454-7211A>T		intron_variant		1		ENSP00000261206	P4
ACSS3	ENST00000549175.1	c.133-7211A>T		intron_variant		5		ENSP00000447748

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135172 AN: 152092 Hom.: 61092 Cov.: 33

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.889 AC: 135251 AN: 152210 Hom.: 61116 Cov.: 33 AF XY: 0.889 AC XY: 66171 AN XY: 74422

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.955

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.926

Alfa AF: 0.924 Hom.: 7678

Bravo AF: 0.880

Asia WGS AF: 0.814 AC: 2826 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.67

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: rs2574742; hg19: chr12-81521384;