rs3811170

Variant names:

• chr12-81077191-T-C
• rs3811170
• ENST00000549175.1:c.-13-32369T>C

Variant summary

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

The ENST00000549175.1(ACSS3):​c.-13-32369T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,312 control chromosomes in the GnomAD database, including 353 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 0.060 (353 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACSS3 ENST00000549175.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000549175.1	c.-13-32369T>C		intron_variant	Intron 2 of 3	5		ENSP00000447748.1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9109 AN: 152194 Hom.: 346 Cov.: 32

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0640

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0600 AC: 9141 AN: 152312 Hom.: 353 Cov.: 32 AF XY: 0.0619 AC XY: 4607 AN XY: 74480

African (AFR) AF: 0.0214 AC: 889 AN: 41570

American (AMR) AF: 0.0392 AC: 599 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.0548 AC: 284 AN: 5182

South Asian (SAS) AF: 0.127 AC: 613 AN: 4828

European-Finnish (FIN) AF: 0.0808 AC: 858 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5270 AN: 68024

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0688 Hom.: 73

Bravo AF: 0.0524

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.35
PhyloP100		-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3811170; hg19: chr12-81470970;