11-68774781-CAAAAAAAAAA-CAAAAAAAAAAAAAAA

Position:

• chr11-68774781-CAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant summary

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

The NM_001876.4(CPT1A):​c.1575+534_1575+535insTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 54,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.000055 (0 hom., cov: 28)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.733

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/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+534_1575+535insTTTTT		intron_variant		ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.1575+534_1575+535insTTTTT		intron_variant		1	NM_001876.4	ENSP00000265641	P1
CPT1A	ENST00000376618.6	c.1575+534_1575+535insTTTTT		intron_variant		1		ENSP00000365803
CPT1A	ENST00000540367.5	c.1575+534_1575+535insTTTTT		intron_variant		1		ENSP00000439084
CPT1A	ENST00000539743.5	c.1575+534_1575+535insTTTTT		intron_variant		5		ENSP00000446108	P1

Frequencies

GnomAD3 genomes AF: 0.0000553 AC: 3 AN: 54260 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000758

Gnomad OTH AF: 0.00145

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

GnomAD4 genome AF: 0.0000553 AC: 3 AN: 54260 Hom.: 0 Cov.: 28 AF XY: 0.0000785 AC XY: 2 AN XY: 25484

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000758

Gnomad4 OTH AF: 0.00145

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 16, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249;