rs80356793

chr11-68780647-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001876.4(CPT1A):c.1451T>C(p.Leu484Pro) variant causes a missense change involving the alteration of a conserved nucleotide. 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 not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1A NM_001876.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 9.05

Genes affected

CPT1A (HGNC:2328): (carnitine palmitoyltransferase 1A) The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (which is located in the outer membrane and is detergent-labile) and carnitine palmitoyltransferase II (which is located in the inner membrane and is detergent-stable), together with a carnitine-acylcarnitine translocase. CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.991

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.1451T>C	p.Leu484Pro	missense_variant	12/19	ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.1451T>C	p.Leu484Pro	missense_variant	12/19	1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.1451T>C	p.Leu484Pro	missense_variant	12/19	1
CPT1A	ENST00000540367.5	c.1451T>C	p.Leu484Pro	missense_variant	11/18	1
CPT1A	ENST00000539743.5	c.1451T>C	p.Leu484Pro	missense_variant	11/18	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
Cadd	Uncertain	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.99	D;D;D;D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Pathogenic	3.7	H;H;H;H
MutationTaster	Benign	1.0	A;A;A;A
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Pathogenic	0.79
Sift	Benign	0.042	D;D;D;D
Sift4G	Uncertain	0.050	T;T;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.95
MutPred		0.94		Loss of stability (P = 0.0275);Loss of stability (P = 0.0275);Loss of stability (P = 0.0275);Loss of stability (P = 0.0275);
MVP		0.99
MPC		0.89
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.93
gMVP		0.99

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

Other links and lift over

dbSNP: rs80356793; hg19: chr11-68548115;