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14-103562995-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001370595.2(COA8):c.-7T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,549,504 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 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

COA8
NM_001370595.2 5_prime_UTR

Scores

2
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.674
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13441801).
BP6
Variant 14-103562995-T-G is Benign according to our data. Variant chr14-103562995-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1681852.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COA8NM_001370595.2 linkuse as main transcriptc.-7T>G 5_prime_UTR_variant 1/5 ENST00000409074.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COA8ENST00000409074.8 linkuse as main transcriptc.-7T>G 5_prime_UTR_variant 1/51 NM_001370595.2 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152066
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000495
AC:
8
AN:
161592
Hom.:
0
AF XY:
0.0000336
AC XY:
3
AN XY:
89364
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000716
AC:
10
AN:
1397438
Hom.:
0
Cov.:
32
AF XY:
0.00000434
AC XY:
3
AN XY:
691266
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000207
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:
9.21e-7
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152066
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 02, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.80
Cadd
Benign
7.5
Dann
Benign
0.56
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0029
N
LIST_S2
Benign
0.15
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.95
T
MutationTaster
Benign
1.0
N
PROVEAN
Pathogenic
-8.6
D
REVEL
Benign
0.021
Sift
Pathogenic
0.0
D
MutPred
0.26
Gain of catalytic residue at G12 (P = 5e-04);
MVP
0.072
ClinPred
0.19
T
GERP RS
-7.2

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: rs1313946521; hg19: chr14-104029332; API