rs141553491
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000098.3(CPT2):c.912G>T(p.Gln304His) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,614,170 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. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
CPT2
NM_000098.3 missense
NM_000098.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 4.41
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_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.110948116).
BP6
?
Variant 1-53210586-G-T is Benign according to our data. Variant chr1-53210586-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 429622.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.912G>T | p.Gln304His | missense_variant | 4/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.912G>T | p.Gln304His | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.912G>T | p.Gln304His | missense_variant | 4/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.286-177C>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152166Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
31
AN:
152166
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251412Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135882
GnomAD3 exomes
AF:
AC:
20
AN:
251412
Hom.:
AF XY:
AC XY:
5
AN XY:
135882
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: 0.0000239 AC: 35AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727244
GnomAD4 exome
AF:
AC:
35
AN:
1461886
Hom.:
Cov.:
31
AF XY:
AC XY:
19
AN XY:
727244
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 ? AF: 0.000210 AC: 32AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74468
GnomAD4 genome
?
AF:
AC:
32
AN:
152284
Hom.:
Cov.:
32
AF XY:
AC XY:
15
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
7
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
15
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Carnitine palmitoyltransferase II deficiency Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The c.912G>T (p.Q304H) alteration is located in exon 4 (coding exon 4) of the CPT2 gene. This alteration results from a G to T substitution at nucleotide position 912, causing the glutamine (Q) at amino acid position 304 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2017 | The Q304H variant has not been published as a pathogenic variant, nor has it been reported as abenign variant to our knowledge. The Q304H variant is observed in 13/10346 (0.13%) alleles fromindividuals of African background in large population cohorts (Lek et al., 2016; 1000 GenomesConsortium et al., 2015; Exome Variant Server). The Q304H variant is a semi-conservative aminoacid substitution, which may impact secondary protein structure as these residues differ in someproperties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistentin its predictions as to whether or not the variant is damaging to the protein structure/function. Insummary, based on the currently available information, it is unclear whether this variant is apathogenic variant or a rare benign variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.
Sift4G
Benign
T;.;.;.;.
Polyphen
B;.;.;.;.
Vest4
MutPred
Loss of ubiquitination at K305 (P = 0.0768);Loss of ubiquitination at K305 (P = 0.0768);Loss of ubiquitination at K305 (P = 0.0768);Loss of ubiquitination at K305 (P = 0.0768);Loss of ubiquitination at K305 (P = 0.0768);
MVP
MPC
ClinPred
T
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