12-81207685-G-T

Position:

• chr12-81207685-G-T

Variant summary

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

The NM_024560.4(ACSS3):​c.1354+8241G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,976 control chromosomes in the GnomAD database, including 11,858 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 0.37 (11858 hom., cov: 32)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS3	NM_024560.4	c.1354+8241G>T		intron_variant		ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6	c.1354+8241G>T		intron_variant		1	NM_024560.4	A1
ACSS3	ENST00000261206.7	c.1351+8241G>T		intron_variant		1		P4
ACSS3	ENST00000546664.2	c.*38+7974G>T		intron_variant, NMD_transcript_variant		5
ACSS3	ENST00000548324.5	n.626+8241G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56522 AN: 151858 Hom.: 11846 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.372 AC: 56550 AN: 151976 Hom.: 11858 Cov.: 32 AF XY: 0.371 AC XY: 27547 AN XY: 74288

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.416

Alfa AF: 0.272 Hom.: 697

Bravo AF: 0.355

Asia WGS AF: 0.263 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.50

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: rs10506274; hg19: chr12-81601464;