rs10492005

chr12-81138883-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 96 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS3	NM_024560.4	c.646-248A>G		intron_variant		ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6	c.646-248A>G		intron_variant		1	NM_024560.4	A1
ACSS3	ENST00000261206.7	c.643-248A>G		intron_variant		1		P4
ACSS3	ENST00000548387.1	n.211-248A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.00464

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0224 Hom.: 51

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10492005; hg19: chr12-81532662;