chr19-49692254-T-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001199753.2(CPT1C):c.2T>G(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
CPT1C
NM_001199753.2 start_lost
NM_001199753.2 start_lost
Scores
8
6
1
Clinical Significance
Conservation
PhyloP100: 6.61
Genes affected
CPT1C (HGNC:18540): (carnitine palmitoyltransferase 1C) This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein regulates the beta-oxidation and transport of long-chain fatty acids into mitochondria, and may play a role in the regulation of feeding behavior and whole-body energy homeostasis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-49692254-T-G is Pathogenic according to our data. Variant chr19-49692254-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 978230.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.2T>G | p.Met1? | start_lost | 3/20 | ENST00000598293.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.2T>G | p.Met1? | start_lost | 3/20 | 2 | NM_001199753.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ExAC
?
AF:
AC:
1
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 73 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Goettingen | Aug 18, 2020 | The CPT1C variant c.2T>G is not found in the gnomAD database and affects the start codon of the CPT1C gene, which may lead to a complete loss of function of the CPT1C protein. Thus, we consider this variant to be likely pathogenic. ACMG criteria used for classification: PVS1, PM2. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D;D;.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Pathogenic
D;D;.;.;D;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;D;.;.;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
D;D;.;D;D;.;.;.
Vest4
MutPred
Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);Gain of methylation at M1 (P = 0.0163);
MVP
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