chr12-81109591-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024560.4(ACSS3):c.343A>G(p.Asn115Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ACSS3
NM_024560.4 missense
NM_024560.4 missense
Scores
7
8
3
Clinical Significance
Conservation
PhyloP100: 8.32
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.887
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACSS3 | NM_024560.4 | c.343A>G | p.Asn115Asp | missense_variant | 2/16 | ENST00000548058.6 | |
LOC107984535 | XR_001749226.2 | n.477+8375T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSS3 | ENST00000548058.6 | c.343A>G | p.Asn115Asp | missense_variant | 2/16 | 1 | NM_024560.4 | A1 | |
ENST00000653205.1 | n.482+8375T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249750Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134954
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460028Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726230
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GnomAD4 genome ? Cov.: 32
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?
Cov.:
32
ExAC
?
AF:
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.343A>G (p.N115D) alteration is located in exon 2 (coding exon 2) of the ACSS3 gene. This alteration results from a A to G substitution at nucleotide position 343, causing the asparagine (N) at amino acid position 115 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.96
MutPred
0.78
.;Loss of helix (P = 0.1299);.;
MVP
MPC
0.83
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at