rs1360046080
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000098.3(CPT2):c.739A>T(p.Arg247Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 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: 6.8e-7 ( 0 hom. )
Consequence
CPT2
NM_000098.3 missense
NM_000098.3 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 2.52
Genes affected
CPT2 (HGNC:2330): (carnitine palmitoyltransferase 2) The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.974
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.739A>T | p.Arg247Trp | missense_variant | 4/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.739A>T | p.Arg247Trp | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.739A>T | p.Arg247Trp | missense_variant | 4/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.286-4T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251146Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135758
GnomAD3 exomes
AF:
AC:
1
AN:
251146
Hom.:
AF XY:
AC XY:
1
AN XY:
135758
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727220
GnomAD4 exome
AF:
AC:
1
AN:
1461840
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727220
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Carnitine palmitoyl transferase II deficiency, severe infantile form Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 17, 2017 | - - |
Carnitine palmitoyl transferase II deficiency, neonatal form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Carnitine palmitoyl transferase II deficiency, myopathic form;C1833511:Carnitine palmitoyl transferase II deficiency, severe infantile form;C1833518:Carnitine palmitoyl transferase II deficiency, neonatal form;C3280160:Encephalopathy, acute, infection-induced, susceptibility to, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 18, 2022 | - - |
Carnitine palmitoyl transferase II deficiency, myopathic form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Encephalopathy, acute, infection-induced, susceptibility to, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.;.
Sift4G
Pathogenic
D;.;.;.;.
Polyphen
D;.;.;.;.
Vest4
MutPred
Loss of ubiquitination at K248 (P = 0.121);Loss of ubiquitination at K248 (P = 0.121);Loss of ubiquitination at K248 (P = 0.121);Loss of ubiquitination at K248 (P = 0.121);Loss of ubiquitination at K248 (P = 0.121);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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