chr11-68775231-ACTACGGTTGGAAAATTCATCTGTAAGACTTCAAATGTGTTTCCCATCCCAGGTAAGTAACAATGGTTGGATAATCCGGACTTAC-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_001876.4(CPT1A):​c.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG variant causes a splice donor, splice region, intron change involving the alteration of a non-conserved nucleotide. 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 DEL_BIG, 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.

Frequency

Genomes: not found (cov: 32)

Consequence

CPT1A
NM_001876.4 splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

0 publications found
Variant links:
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, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.0503876 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPT1ANM_001876.4 linkc.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG splice_donor_variant, splice_region_variant, intron_variant Intron 13 of 18 ENST00000265641.10 NP_001867.2 P50416-1A0A024R5F4Q8WZ48B2RAQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPT1AENST00000265641.10 linkc.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG splice_donor_variant, splice_region_variant, intron_variant Intron 13 of 18 1 NM_001876.4 ENSP00000265641.4 P50416-1
CPT1AENST00000376618.6 linkc.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG splice_donor_variant, splice_region_variant, intron_variant Intron 13 of 18 1 ENSP00000365803.2 P50416-2
CPT1AENST00000540367.5 linkc.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG splice_donor_variant, splice_region_variant, intron_variant Intron 12 of 17 1 ENSP00000439084.1 P50416-2
CPT1AENST00000539743.5 linkc.1575+1_1575+84delGTAAGTCCGGATTATCCAACCATTGTTACTTACCTGGGATGGGAAACACATTTGAAGTCTTACAGATGAATTTTCCAACCGTAG splice_donor_variant, splice_region_variant, intron_variant Intron 12 of 17 5 ENSP00000446108.1 P50416-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.4

Splicing

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

Publications

Other links and lift over

dbSNP: rs80356802; hg19: chr11-68542699; API