14-103563002-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_001370595.2(COA8):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,557,770 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001370595.2 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COA8 | NM_001370595.2 | c.1A>G | p.Met1? | start_lost | Exon 1 of 5 | ENST00000409074.8 | NP_001357524.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COA8 | ENST00000409074.8 | c.1A>G | p.Met1? | start_lost | Exon 1 of 5 | 1 | NM_001370595.2 | ENSP00000386485.3 | ||
ENSG00000256500 | ENST00000472726.3 | c.1A>G | p.Met1? | start_lost | Exon 1 of 18 | 2 | ENSP00000439065.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 35
GnomAD4 exome AF: 0.00000640 AC: 9AN: 1405582Hom.: 1 Cov.: 32 AF XY: 0.00000719 AC XY: 5AN XY: 695880
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.40A>G (p.M14V) alteration is located in exon 1 (coding exon 1) of the APOPT1 gene. This alteration results from a A to G substitution at nucleotide position 40, causing the methionine (M) at amino acid position 14 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 14 of the APOPT1 protein (p.Met14Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APOPT1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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