rs80356780
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_001876.4(CPT1A):c.2129G>A(p.Gly710Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G710R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001876.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT1A | NM_001876.4 | c.2129G>A | p.Gly710Glu | missense_variant | 17/19 | ENST00000265641.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT1A | ENST00000265641.10 | c.2129G>A | p.Gly710Glu | missense_variant | 17/19 | 1 | NM_001876.4 | P1 | |
CPT1A | ENST00000376618.6 | c.2129G>A | p.Gly710Glu | missense_variant | 17/19 | 1 | |||
CPT1A | ENST00000540367.5 | c.2129G>A | p.Gly710Glu | missense_variant | 16/18 | 1 | |||
CPT1A | ENST00000539743.5 | c.2129G>A | p.Gly710Glu | missense_variant | 16/18 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000815 AC: 2AN: 245462Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132696
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457638Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724782
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Carnitine palmitoyl transferase 1A deficiency Pathogenic:3Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 17, 2023 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects CPT1A function (PMID: 11350182). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPT1A protein function. ClinVar contains an entry for this variant (Variation ID: 9071). This missense change has been observed in individual(s) with carnitine palmitoyltransferase 1A deficiency (PMID: 11350183). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs80356780, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 710 of the CPT1A protein (p.Gly710Glu). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2001 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 09, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 14, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at