rs770734793
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000098.3(CPT2):c.1429C>T(p.Arg477Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,948 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R477Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.1429C>T | p.Arg477Trp | missense_variant | Exon 4 of 5 | ENST00000371486.4 | NP_000089.1 | |
CPT2 | NM_001330589.2 | c.1429C>T | p.Arg477Trp | missense_variant | Exon 4 of 5 | NP_001317518.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250864Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135670
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461722Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26AN XY: 727158
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
Carnitine palmitoyltransferase II deficiency Uncertain:2
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 477 of the CPT2 protein (p.Arg477Trp). This variant is present in population databases (rs770734793, gnomAD 0.005%). This missense change has been observed in individuals with CTP2 deficiency (PMID: 29552494, 31372341). ClinVar contains an entry for this variant (Variation ID: 577988). 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 not expected to disrupt CPT2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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Carnitine palmitoyl transferase II deficiency, neonatal form Uncertain:1
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Carnitine palmitoyl transferase II deficiency, myopathic form;C1833511:Carnitine palmitoyl transferase II deficiency, severe infantile form;C1833518:Carnitine palmitoyl transferase II deficiency, neonatal form;C3280160:Encephalopathy, acute, infection-induced, susceptibility to, 4 Uncertain:1
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Carnitine palmitoyl transferase II deficiency, myopathic form Uncertain:1
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Encephalopathy, acute, infection-induced, susceptibility to, 4 Uncertain:1
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Carnitine palmitoyl transferase II deficiency, severe infantile form Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at