19-49700693-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001199753.2(CPT1C):c.291A>C(p.Gln97His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,608,866 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 2 hom. )

Consequence

CPT1C
NM_001199753.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.52

Publications

4 publications found

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]

CPT1C Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 73
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CPT1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006986916).

BP6

Variant 19-49700693-A-C is Benign according to our data. Variant chr19-49700693-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 542769.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 82 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199753.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPT1C	NM_001199753.2	MANE Select	c.291A>C	p.Gln97His	missense	Exon 5 of 20	NP_001186682.1	Q8TCG5-1
CPT1C	NM_001378482.1		c.291A>C	p.Gln97His	missense	Exon 5 of 19	NP_001365411.1
CPT1C	NM_001199752.3		c.291A>C	p.Gln97His	missense	Exon 5 of 20	NP_001186681.1	Q8TCG5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPT1C	ENST00000598293.6	TSL:2 MANE Select	c.291A>C	p.Gln97His	missense	Exon 5 of 20	ENSP00000473028.1	Q8TCG5-1
CPT1C	ENST00000323446.9	TSL:1	c.291A>C	p.Gln97His	missense	Exon 4 of 19	ENSP00000319343.4	Q8TCG5-1
CPT1C	ENST00000405931.6	TSL:1	c.291A>C	p.Gln97His	missense	Exon 5 of 20	ENSP00000384465.2	Q8TCG5-2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000498

AC:

123

AN:

247186

AF XY:

0.000567

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.000512

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000400

AC:

582

AN:

1456562

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

303

AN XY:

724858

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33470

American (AMR)

AF:

0.0000671

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00313

AC:

151

AN:

48266

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000365

AC:

406

AN:

1111964

Other (OTH)

AF:

0.000265

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000538

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41580

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00386

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68020

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000593

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000453

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CPT1C-related disorder (1)

Hereditary spastic paraplegia 73 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.16

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.72

M_CAP

Benign

0.052

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.0

PhyloP100

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

REVEL

Benign

0.20

Sift

Benign

0.56

Sift4G

Benign

0.57

Polyphen

0.080

Vest4

0.26

MutPred

0.28

Gain of disorder (P = 0.0943)

MVP

0.48

MPC

0.48

ClinPred

0.022

GERP RS

1.1

Varity_R

0.059

gMVP

0.74

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over