rs775472956

Variant names:

• chr12-81078203-G-A
• rs775472956
• NM_024560.4:c.83G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-81078203-G-A
• chr12-81078203-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024560.4(ACSS3):​c.83G>A​(p.Arg28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,413,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACSS3 NM_024560.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14141673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS3	NM_024560.4	c.83G>A	p.Arg28Gln	missense_variant	Exon 1 of 16	ENST00000548058.6	NP_078836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS3	ENST00000548058.6	c.83G>A	p.Arg28Gln	missense_variant	Exon 1 of 16	1	NM_024560.4	ENSP00000449535.1
ACSS3	ENST00000261206.7	c.83G>A	p.Arg28Gln	missense_variant	Exon 1 of 16	1		ENSP00000261206.3
ACSS3	ENST00000549175.1	c.-13-31357G>A		intron_variant	Intron 2 of 3	5		ENSP00000447748.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1413616 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700670

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.038
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.79	P;.
Vest4		0.25
MutPred		0.24		Loss of methylation at R28 (P = 0.0057);Loss of methylation at R28 (P = 0.0057);
MVP		0.040
MPC		0.79
ClinPred		0.65	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775472956; hg19: chr12-81471982;