chr12-81081854-G-C

Variant names:

• chr12-81081854-G-C
• rs7138951
• NM_024560.4:c.311+3423G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024560.4(ACSS3):​c.311+3423G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ACSS3 NM_024560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.311+3423G>C		intron_variant	Intron 1 of 15	ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.311+3423G>C		intron_variant	Intron 1 of 15	1	NM_024560.4	ENSP00000449535.1
ACSS3	ENST00000261206.7	c.308+3426G>C		intron_variant	Intron 1 of 15	1		ENSP00000261206.3
ACSS3	ENST00000549175.1	c.-13-27706G>C		intron_variant	Intron 2 of 3	5		ENSP00000447748.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.27
PhyloP100		0.74

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: rs7138951; hg19: chr12-81475633;