M-9309-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The ENST00000362079.2(MT-CO3):āc.103T>Cā(p.Phe35Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F35S) has been classified as Likely benign.
Frequency
Mitomap GenBank:
š 0.00010 ( AC: 9 )
Consequence
MT-CO3
ENST00000362079.2 missense
ENST00000362079.2 missense
Scores
Apogee2
Benign
Clinical Significance
No linked disesase in Mitomap
Conservation
PhyloP100: 4.70
Genes affected
MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Apogee2 supports a benign effect, 0.10256419 < 0.5 .
BS2
High AC in GnomadMitoHomoplasmic at 4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COX3 | COX3.1 use as main transcript | c.103T>C | p.Phe35Leu | missense_variant | 1/1 | YP_003024032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MT-CO3 | ENST00000362079.2 | c.103T>C | p.Phe35Leu | missense_variant | 1/1 | ENSP00000354982 | P1 |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
9
Gnomad homoplasmic
AF:
AC:
4
AN:
56430
Gnomad heteroplasmic
AF:
AC:
1
AN:
56430
Alfa
AF:
Hom.:
Mitomap
No disease associated.
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Leigh syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Oct 17, 2019 | The NC_012920.1:m.9309T>C (YP_003024032.1:p.Phe35Leu) variant in MTCO3 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
Hmtvar
Pathogenic
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
DEOGEN2
Benign
T
LIST_S2
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PROVEAN
Pathogenic
D
Sift
Pathogenic
D
Sift4G
Uncertain
D
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at