rs113511313

Positions:

• chr19-49713585-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001199753.2(CPT1C):​c.2392A>G​(p.Met798Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,116 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (18 hom.)
• Consequence: CPT1C NM_001199753.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0750

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049996674).
• BP6: Variant 19-49713585-A-G is Benign according to our data. Variant chr19-49713585-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 542770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49713585-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00232 (353/152298) while in subpopulation NFE AF= 0.00365 (248/68024). AF 95% confidence interval is 0.00327. There are 1 homozygotes in gnomad4. There are 173 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 353 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1C	NM_001199753.2	c.2392A>G	p.Met798Val	missense_variant	20/20	ENST00000598293.6	NP_001186682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1C	ENST00000598293.6	c.2392A>G	p.Met798Val	missense_variant	20/20	2	NM_001199753.2	ENSP00000473028.1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 353 AN: 152180 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00273 AC: 678 AN: 248456 Hom.: 1 AF XY: 0.00277 AC XY: 372 AN XY: 134374

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00145

Gnomad FIN exome AF: 0.00409

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00413

GnomAD4 exome AF: 0.00358 AC: 5228 AN: 1459818 Hom.: 18 Cov.: 31 AF XY: 0.00348 AC XY: 2528 AN XY: 726286

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.000610

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.00424

Gnomad4 NFE exome AF: 0.00413

Gnomad4 OTH exome AF: 0.00350

GnomAD4 genome AF: 0.00232 AC: 353 AN: 152298 Hom.: 1 Cov.: 31 AF XY: 0.00232 AC XY: 173 AN XY: 74474

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00314 Hom.: 1

Bravo AF: 0.00216

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00304 AC: 369

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 73 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Jan 01, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.33
DANN	Benign	0.28
DEOGEN2	Benign	0.045	T;T;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.36	.;.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0050	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.34	N;N;N;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.30	N;N;.;N;.
REVEL	Benign	0.13
Sift	Benign	0.76	T;T;.;T;.
Sift4G	Benign	0.76	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.14
MVP		0.45
MPC		0.39
ClinPred		0.00030	T
GERP RS		1.4
Varity_R		0.019
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs113511313; hg19: chr19-50216842; COSMIC: COSV54921363; COSMIC: COSV54921363;