rs10860

Variant names:

• chr12-81256581-C-A
• rs10860
• NM_024560.4:c.*1659C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024560.4(ACSS3):​c.*1659C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,096 control chromosomes in the GnomAD database, including 390 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 0.053 (390 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ACSS3 NM_024560.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 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.*1659C>A		3_prime_UTR	Exon 16 of 16	NP_078836.1
	ACSS3	NM_001330242.2		c.*1659C>A		3_prime_UTR	Exon 16 of 16	NP_001317171.1
	ACSS3	NM_001330243.2		c.*1659C>A		3_prime_UTR	Exon 17 of 17	NP_001317172.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.*1659C>A		3_prime_UTR	Exon 16 of 16	ENSP00000449535.1
	ACSS3	ENST00000965760.1		c.*1659C>A		3_prime_UTR	Exon 16 of 16	ENSP00000635819.1
	ACSS3	ENST00000903501.1		c.*1659C>A		3_prime_UTR	Exon 15 of 15	ENSP00000573560.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8013 AN: 151978 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0492

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0528 AC: 8034 AN: 152096 Hom.: 390 Cov.: 32 AF XY: 0.0544 AC XY: 4046 AN XY: 74352

African (AFR) AF: 0.129 AC: 5329 AN: 41460

American (AMR) AF: 0.0275 AC: 420 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.0450 AC: 232 AN: 5160

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4822

European-Finnish (FIN) AF: 0.0563 AC: 596 AN: 10588

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0176 AC: 1198 AN: 68002

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0320 Hom.: 46

Bravo AF: 0.0545

Asia WGS AF: 0.0280 AC: 98 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.44
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: rs10860; hg19: chr12-81650360;