rs200190780

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001199753.2(CPT1C):ā€‹c.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

Scores

4
9
6

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 5.73
Variant links:
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]

Genome browser will be placed here

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
CPT1CNM_001199753.2 linkuse as main transcriptc.2059C>G p.Pro687Ala missense_variant 18/20 ENST00000598293.6 NP_001186682.1 Q8TCG5-1A0A024QZE3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CPT1CENST00000598293.6 linkuse as main transcriptc.2059C>G p.Pro687Ala missense_variant 18/202 NM_001199753.2 ENSP00000473028.1 Q8TCG5-1

Frequencies

GnomAD3 genomes
AF:
0.000473
AC:
72
AN:
152086
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000912
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000350
AC:
88
AN:
251460
Hom.:
0
AF XY:
0.000353
AC XY:
48
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000730
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000737
AC:
1078
AN:
1461842
Hom.:
2
Cov.:
31
AF XY:
0.000723
AC XY:
526
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.000942
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000473
AC:
72
AN:
152204
Hom.:
0
Cov.:
30
AF XY:
0.000497
AC XY:
37
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000912
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000750
Hom.:
0
Bravo
AF:
0.000276
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000280
AC:
34
EpiCase
AF:
0.000491
EpiControl
AF:
0.000652

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 submitterclinical testingAmbry GeneticsJun 18, 2021The 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 providedclinical testingPreventionGenetics, part of Exact SciencesJul 24, 2023This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;D;D;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
.;.;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Uncertain
0.60
D
MutationAssessor
Benign
1.9
L;L;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-6.0
D;D;.;D
REVEL
Pathogenic
0.65
Sift
Benign
0.038
D;D;.;D
Sift4G
Uncertain
0.037
D;D;D;D
Polyphen
0.96
D;D;D;D
Vest4
0.50
MVP
0.93
MPC
1.2
ClinPred
0.52
D
GERP RS
4.6
Varity_R
0.37
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200190780; hg19: chr19-50216032; API