chr14-103563041-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001370595.2(COA8):c.40C>T(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,543,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 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. P14A) has been classified as Benign.
Frequency
Consequence
NM_001370595.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COA8 | NM_001370595.2 | c.40C>T | p.Pro14Ser | missense_variant | 1/5 | ENST00000409074.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COA8 | ENST00000409074.8 | c.40C>T | p.Pro14Ser | missense_variant | 1/5 | 1 | NM_001370595.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152102Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000277 AC: 4AN: 144426Hom.: 0 AF XY: 0.0000126 AC XY: 1AN XY: 79108
GnomAD4 exome AF: 0.0000122 AC: 17AN: 1391556Hom.: 0 Cov.: 38 AF XY: 0.0000131 AC XY: 9AN XY: 687708
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74424
ClinVar
Submissions by phenotype
Mitochondrial complex 4 deficiency, nuclear type 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 03, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 1061664). This variant has not been reported in the literature in individuals affected with APOPT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 27 of the APOPT1 protein (p.Pro27Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at