11-68807553-G-C

Variant names:

• chr11-68807553-G-C
• NM_001876.4:c.367C>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.367C>G​(p.Arg123Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPT1A NM_001876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

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, 0.953

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.367C>G	p.Arg123Gly	missense_variant	Exon 4 of 19	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.367C>G	p.Arg123Gly	missense_variant	Exon 4 of 19	1	NM_001876.4	ENSP00000265641.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.94	.;.;D;D;D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	.;D;.;D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	3.1	M;M;M;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.6	D;D;D;D;D
REVEL	Pathogenic	0.96
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;.
Polyphen		1.0	D;D;D;D;.
Vest4		0.93
MutPred		0.82		Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);
MVP		0.97
MPC		1.4
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.72
gMVP		0.97

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: chr11-68575021;