11-68794819-CC-TT

Variant names:

• chr11-68794819-CC-TT
• NM_001876.4:c.863_864delGGinsAA
• CPT1A p.Arg288Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001876.4(CPT1A):​c.863_864delGGinsAA​(p.Arg288Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R288W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1A NM_001876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

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]

CPT1A Gene-Disease associations (from GenCC):

• carnitine palmitoyl transferase 1A deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	NP_001867.2	P50416-1
	CPT1A	NM_001440358.1		c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	NP_001427288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	ENSP00000265641.4	P50416-1
	CPT1A	ENST00000376618.6	TSL:1	c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	ENSP00000365803.2	P50416-2
	CPT1A	ENST00000540367.5	TSL:1	c.863_864delGGinsAA	p.Arg288Gln	missense	N/A	ENSP00000439084.1	P50416-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-68562287;