rs10492005

Variant names:

• chr12-81138883-A-G
• rs10492005
• NM_024560.4:c.646-248A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024560.4(ACSS3):​c.646-248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,302 control chromosomes in the GnomAD database, including 96 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 0.023 (96 hom., cov: 32)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0229 (3492/152302) while in subpopulation NFE AF = 0.0272 (1849/68026). AF 95% confidence interval is 0.0261. There are 96 homozygotes in GnomAd4. There are 1958 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 96 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.646-248A>G		intron_variant	Intron 3 of 15	ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.646-248A>G		intron_variant	Intron 3 of 15	1	NM_024560.4	ENSP00000449535.1
ACSS3	ENST00000261206.7	c.643-248A>G		intron_variant	Intron 3 of 15	1		ENSP00000261206.3
ACSS3	ENST00000548387.1	n.211-248A>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3491 AN: 152184 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0229 AC: 3492 AN: 152302 Hom.: 96 Cov.: 32 AF XY: 0.0263 AC XY: 1958 AN XY: 74478

African (AFR) AF: 0.00464 AC: 193 AN: 41558

American (AMR) AF: 0.0116 AC: 178 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4830

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1849 AN: 68026

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0224 Hom.: 60

Bravo AF: 0.0147

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.54
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10492005; hg19: chr12-81532662;