14-103563025-G-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001370595.2(COA8):c.24G>A(p.Lys8Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,555,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
COA8
NM_001370595.2 synonymous
NM_001370595.2 synonymous
Scores
13
Clinical Significance
Conservation
PhyloP100: -1.63
Genes affected
COA8 (HGNC:20492): (cytochrome c oxidase assembly factor 8) This gene encodes a protein that localizes to the mitochondria, where it stimulates the release of cytochrome c, thereby promoting programmed cell death. Mutations in this gene have been found in individuals with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07327938).
BP6
Variant 14-103563025-G-A is Benign according to our data. Variant chr14-103563025-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3705706.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.63 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COA8 | NM_001370595.2 | c.24G>A | p.Lys8Lys | synonymous_variant | 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.24G>A | p.Lys8Lys | synonymous_variant | Exon 1 of 5 | 1 | NM_001370595.2 | ENSP00000386485.3 | ||
ENSG00000256500 | ENST00000472726.3 | c.24G>A | p.Lys8Lys | synonymous_variant | Exon 1 of 18 | 2 | ENSP00000439065.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000248 AC: 4AN: 161356Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 88542
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GnomAD4 exome AF: 0.0000606 AC: 85AN: 1403726Hom.: 0 Cov.: 32 AF XY: 0.0000533 AC XY: 37AN XY: 694734
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
MutPred
Gain of catalytic residue at L23 (P = 0);
MVP
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at