chrM-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):ā€‹c.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

Scores

Apogee2
Benign
0.10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1
No linked disesase in Mitomap

Conservation

PhyloP100: 4.70
Variant links:
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
COX3COX3.1 use as main transcriptc.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-CO3ENST00000362079.2 linkuse as main transcriptc.103T>C p.Phe35Leu missense_variant 1/1 ENSP00000354982 P1

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.00010
AC:
9
Gnomad homoplasmic
AF:
0.000071
AC:
4
AN:
56430
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56430
Alfa
AF:
0.000223
Hom.:
1

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 submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineOct 17, 2019The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.10
Hmtvar
Pathogenic
0.68
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Benign
-0.22
T
DEOGEN2
Benign
0.085
T
LIST_S2
Benign
0.69
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
N
PROVEAN
Pathogenic
-4.7
D
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0080
D
GERP RS
5.0
Varity_R
0.68

Splicing

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: rs1603222236; hg19: chrM-9310; API