19-49692359-T-G

Position:

• chr19-49692359-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001199753.2(CPT1C):​c.107T>G​(p.Leu36Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CPT1C NM_001199753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1C	NM_001199753.2	c.107T>G	p.Leu36Arg	missense_variant	3/20	ENST00000598293.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1C	ENST00000598293.6	c.107T>G	p.Leu36Arg	missense_variant	3/20	2	NM_001199753.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 73 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2022

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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CPT1C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 36 of the CPT1C protein (p.Leu36Arg). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;D;D;D;.;.;D;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.7	L;L;.;L;L;.;.;.
MutationTaster	Benign	0.90	D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.1	D;D;.;.;D;.;.;.
REVEL	Pathogenic	0.70
Sift	Benign	0.066	T;T;.;.;T;.;.;.
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D;D
Polyphen		0.25	B;B;.;B;B;.;.;.
Vest4		0.79
MutPred		0.67		Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);Gain of disorder (P = 0.0269);
MVP		0.88
MPC		1.5
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.76
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50195616;