19-49692307-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001199753.2(CPT1C):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A19V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001199753.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT1C | NM_001199753.2 | c.55G>A | p.Ala19Thr | missense_variant | 3/20 | ENST00000598293.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT1C | ENST00000598293.6 | c.55G>A | p.Ala19Thr | missense_variant | 3/20 | 2 | NM_001199753.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251306Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135858
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.55G>A (p.A19T) alteration is located in exon 3 (coding exon 1) of the CPT1C gene. This alteration results from a G to A substitution at nucleotide position 55, causing the alanine (A) at amino acid position 19 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2018 | This sequence change replaces alanine with threonine at codon 19 of the CPT1C protein (p.Ala19Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CPT1C-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at