NM_020312.4:c.37G>A
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_020312.4(COQ9):c.37G>A(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,308,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. A13G) has been classified as Uncertain significance.
Frequency
Consequence
NM_020312.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COQ9 | NM_020312.4 | c.37G>A | p.Ala13Thr | missense_variant | Exon 1 of 9 | ENST00000262507.11 | NP_064708.1 | |
CIAPIN1 | NM_020313.4 | c.-256C>T | upstream_gene_variant | ENST00000394391.9 | NP_064709.2 | |||
CIAPIN1 | NM_001308347.2 | c.-256C>T | upstream_gene_variant | NP_001295276.1 | ||||
CIAPIN1 | NM_001308358.2 | c.-256C>T | upstream_gene_variant | NP_001295287.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.0000195 AC: 1AN: 51266 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000216 AC: 25AN: 1156388Hom.: 0 Cov.: 31 AF XY: 0.0000215 AC XY: 12AN XY: 557570 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152358Hom.: 0 Cov.: 34 AF XY: 0.0000268 AC XY: 2AN XY: 74504 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.37G>A (p.A13T) alteration is located in exon 1 (coding exon 1) of the COQ9 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 13 of the COQ9 protein (p.Ala13Thr). 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 COQ9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. -
Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome Benign:1
The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at