11-68757723-T-C

Variant names:

• chr11-68757723-T-C
• NM_001876.4:c.2243A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001876.4(CPT1A):​c.2243A>G​(p.His748Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,936 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPT1A NM_001876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 19	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 19	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.2235+1846A>G		intron_variant	Intron 18 of 18	1		ENSP00000365803.2
CPT1A	ENST00000540367.5	c.2235+1846A>G		intron_variant	Intron 17 of 17	1		ENSP00000439084.1
CPT1A	ENST00000539743.5	c.2243A>G	p.His748Arg	missense_variant	Exon 18 of 18	5		ENSP00000446108.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460936 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Pathogenic	0.82	D;D
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.0030
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Uncertain	-0.032	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Pathogenic	0.69
Sift	Benign	0.24	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.13	B;B
Vest4		0.43
MutPred		0.46		Gain of phosphorylation at S747 (P = 0.0877);Gain of phosphorylation at S747 (P = 0.0877);
MVP		0.94
MPC		0.53
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.54

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: chr11-68525191;