16-20564724-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001105069.2(ACSM2B):c.122C>T(p.Pro41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,613,250 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 1 hom. )
Consequence
ACSM2B
NM_001105069.2 missense
NM_001105069.2 missense
Scores
5
5
8
Clinical Significance
Conservation
PhyloP100: 4.33
Genes affected
ACSM2B (HGNC:30931): (acyl-CoA synthetase medium chain family member 2B) Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [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, 0.851
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACSM2B | NM_001105069.2 | c.122C>T | p.Pro41Leu | missense_variant | 2/14 | ENST00000329697.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSM2B | ENST00000329697.10 | c.122C>T | p.Pro41Leu | missense_variant | 2/14 | 1 | NM_001105069.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000132 AC: 20AN: 151992Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248406Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134284
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461258Hom.: 1 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 726926
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GnomAD4 genome ? AF: 0.000132 AC: 20AN: 151992Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7AN XY: 74240
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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 | Dec 01, 2022 | The c.122C>T (p.P41L) alteration is located in exon 3 (coding exon 1) of the ACSM2B gene. This alteration results from a C to T substitution at nucleotide position 122, causing the proline (P) at amino acid position 41 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;.
Polyphen
D;D;D;D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at