14-103563025-G-A

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

Scores

13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63
Variant links:
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]

Genome browser will be placed here

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
COA8NM_001370595.2 linkc.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
COA8ENST00000409074.8 linkc.24G>A p.Lys8Lys synonymous_variant Exon 1 of 5 1 NM_001370595.2 ENSP00000386485.3 A0A6Q8JUI0
ENSG00000256500ENST00000472726.3 linkc.24G>A p.Lys8Lys synonymous_variant Exon 1 of 18 2 ENSP00000439065.2 E7EVH7

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152236
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000248
AC:
4
AN:
161356
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
88542
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000364
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000299
Gnomad OTH exome
AF:
0.000220
GnomAD4 exome
AF:
0.0000606
AC:
85
AN:
1403726
Hom.:
0
Cov.:
32
AF XY:
0.0000533
AC XY:
37
AN XY:
694734
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000257
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000753
Gnomad4 OTH exome
AF:
0.0000342
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152236
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000176
AC:
2

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.5
DANN
Benign
0.88
Eigen
Benign
-0.89
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0050
N
LIST_S2
Benign
0.32
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.090
N
REVEL
Benign
0.090
Sift
Benign
0.39
T
MutPred
0.39
Gain of catalytic residue at L23 (P = 0);
MVP
0.030
ClinPred
0.10
T
GERP RS
-3.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs757218281; hg19: chr14-104029362; API