rs1131691925
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000098.3(CPT2):c.371G>A(p.Arg124Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,342 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.371G>A | p.Arg124Gln | missense_variant | 4/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.371G>A | p.Arg124Gln | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.371G>A | p.Arg124Gln | missense_variant | 4/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.573C>T | non_coding_transcript_exon_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151476Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251362Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151476Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73938
ClinVar
Submissions by phenotype
Carnitine palmitoyltransferase II deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 18, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 CPT2 protein function. ClinVar contains an entry for this variant (Variation ID: 553350). This missense change has been observed in individual(s) with carnitine palmitoyltransferase II (CPTII or CPT2) deficiency (PMID: 12673791). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 124 of the CPT2 protein (p.Arg124Gln). - |
Carnitine palmitoyl transferase II deficiency, severe infantile form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Aug 22, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at