chr19-49697341-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001199753.2(CPT1C):c.157G>A(p.Gly53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,936 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 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
CPT1C
NM_001199753.2 missense
NM_001199753.2 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 6.95
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 Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851
BS2
High AC in GnomAdExome4 at 39 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.157G>A | p.Gly53Ser | missense_variant | 4/20 | ENST00000598293.6 | NP_001186682.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.157G>A | p.Gly53Ser | missense_variant | 4/20 | 2 | NM_001199753.2 | ENSP00000473028 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152102Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251426Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135874
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727214
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152102Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74284
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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 | Aug 04, 2021 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CPT1C-related conditions. This variant is present in population databases (rs374236576, ExAC 0.004%). This sequence change replaces glycine with serine at codon 53 of the CPT1C protein (p.Gly53Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;T;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;M;.;M;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;.;.;D;.;.;.
REVEL
Pathogenic
Sift
Benign
T;T;.;.;T;.;.;.
Sift4G
Benign
T;T;D;T;T;D;T;T
Polyphen
D;D;.;D;D;.;.;.
Vest4
MutPred
Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);Loss of catalytic residue at G53 (P = 0.0588);
MVP
MPC
1.1
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at