12-81207685-G-T

Variant names:

• chr12-81207685-G-T
• rs10506274
• NM_024560.4:c.1354+8241G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	NM_024560.4	MANE Select	c.1354+8241G>T		intron	N/A	NP_078836.1	Q9H6R3-1
	ACSS3	NM_001330242.2		c.1351+8241G>T		intron	N/A	NP_001317171.1	A0A0B4J1R2
	ACSS3	NM_001330243.2		c.400+8241G>T		intron	N/A	NP_001317172.1	Q9H6R3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.1354+8241G>T		intron	N/A	ENSP00000449535.1	Q9H6R3-1
	ACSS3	ENST00000261206.7	TSL:1	c.1351+8241G>T		intron	N/A	ENSP00000261206.3	A0A0B4J1R2
	ACSS3	ENST00000965760.1		c.1351+8241G>T		intron	N/A	ENSP00000635819.1

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

African (AFR) AF: 0.201 AC: 8331 AN: 41464

American (AMR) AF: 0.342 AC: 5219 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3466

East Asian (EAS) AF: 0.141 AC: 730 AN: 5178

South Asian (SAS) AF: 0.394 AC: 1892 AN: 4808

European-Finnish (FIN) AF: 0.465 AC: 4913 AN: 10564

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32380 AN: 67934

Other (OTH) AF: 0.416 AC: 874 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.50
PhyloP100		0.65
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: rs10506274; hg19: chr12-81601464; COSMIC: COSV108086756;