rs577177807
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_001199753.2(CPT1C):c.1384G>A(p.Gly462Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,884 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: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
CPT1C
NM_001199753.2 missense
NM_001199753.2 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 9.69
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 Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.1384G>A | p.Gly462Arg | missense_variant | 13/20 | ENST00000598293.6 | NP_001186682.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.1384G>A | p.Gly462Arg | missense_variant | 13/20 | 2 | NM_001199753.2 | ENSP00000473028.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251186Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135764
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461640Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727112
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74454
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2017 | This sequence change replaces glycine with arginine at codon 451 of the CPT1C protein (p.Gly451Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs577177807, ExAC 0.02%) but has not been reported in the literature in individuals with a CPT1C-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D;D;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;D;.
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0377);Gain of MoRF binding (P = 0.0377);Gain of MoRF binding (P = 0.0377);.;.;
MVP
MPC
1.3
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: -40
Find out detailed SpliceAI scores and Pangolin per-transcript scores at