rs200190780
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001199753.2(CPT1C):āc.2059C>Gā(p.Pro687Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000712 in 1,614,046 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00047 ( 0 hom., cov: 30)
Exomes š: 0.00074 ( 2 hom. )
Consequence
CPT1C
NM_001199753.2 missense
NM_001199753.2 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 5.73
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 Benign. Variant got -9 ACMG points.
BP6
Variant 19-49712775-C-G is Benign according to our data. Variant chr19-49712775-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 542768.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000473 (72/152204) while in subpopulation NFE AF= 0.000912 (62/68004). AF 95% confidence interval is 0.000729. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 72 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.2059C>G | p.Pro687Ala | missense_variant | 18/20 | ENST00000598293.6 | NP_001186682.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.2059C>G | p.Pro687Ala | missense_variant | 18/20 | 2 | NM_001199753.2 | ENSP00000473028.1 |
Frequencies
GnomAD3 genomes AF: 0.000473 AC: 72AN: 152086Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000350 AC: 88AN: 251460Hom.: 0 AF XY: 0.000353 AC XY: 48AN XY: 135908
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GnomAD4 exome AF: 0.000737 AC: 1078AN: 1461842Hom.: 2 Cov.: 31 AF XY: 0.000723 AC XY: 526AN XY: 727224
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GnomAD4 genome AF: 0.000473 AC: 72AN: 152204Hom.: 0 Cov.: 30 AF XY: 0.000497 AC XY: 37AN XY: 74418
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.2059C>G (p.P687A) alteration is located in exon 18 (coding exon 16) of the CPT1C gene. This alteration results from a C to G substitution at nucleotide position 2059, causing the proline (P) at amino acid position 687 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
CPT1C-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 24, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary spastic paraplegia 73 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D
REVEL
Pathogenic
Sift
Benign
D;D;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
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