19-49708814-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001199753.2(CPT1C):c.1541G>A(p.Arg514Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 1,613,024 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R514L) has been classified as Benign.
Frequency
Consequence
NM_001199753.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.1541G>A | p.Arg514Gln | missense_variant | 14/20 | ENST00000598293.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.1541G>A | p.Arg514Gln | missense_variant | 14/20 | 2 | NM_001199753.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 151886Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000267 AC: 67AN: 250992Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135712
GnomAD4 exome AF: 0.000641 AC: 936AN: 1461020Hom.: 1 Cov.: 30 AF XY: 0.000630 AC XY: 458AN XY: 726892
GnomAD4 genome AF: 0.000263 AC: 40AN: 152004Hom.: 0 Cov.: 30 AF XY: 0.000135 AC XY: 10AN XY: 74332
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 503 of the CPT1C protein (p.Arg503Gln). This variant is present in population databases (rs150853576, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CPT1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 542767). 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 CPT1C 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at