M-9247-G-A

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000362079.2(MT-CO3):​c.41G>A​(p.Ser14Asn) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14T) has been classified as Uncertain significance.

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 0 )

Consequence

MT-CO3
ENST00000362079.2 missense

Scores

Apogee2
Pathogenic
0.57

Clinical Significance

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

Conservation

PhyloP100: 7.72
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]
MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very low frequency in mitomap database: 0.0
PP3
Apogee2 supports a deletorius effect, 0.5747469 >= 0.5 .

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX3COX3.1 use as main transcriptc.41G>A p.Ser14Asn missense_variant 1/1 YP_003024032.1
ATP6ATP6.1 use as main transcript downstream_gene_variant YP_003024031.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-CO3ENST00000362079.2 linkuse as main transcriptc.41G>A p.Ser14Asn missense_variant 1/1 ENSP00000354982 P1
MT-ATP6ENST00000361899.2 linkuse as main transcript downstream_gene_variant ENSP00000354632 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:
0.0
AC:
0
Gnomad homoplasmic
AF:
0.0
AC:
0
AN:
56420
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56420

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.9247G>A (YP_003024032.1:p.Ser14Asn) 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: PP6, PP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Pathogenic
0.57
Hmtvar
Pathogenic
0.73
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.14
T
DEOGEN2
Benign
0.16
T
LIST_S2
Uncertain
0.91
D
MutationAssessor
Pathogenic
4.7
H
MutationTaster
Benign
1.0
N
PROVEAN
Uncertain
-2.6
D
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0080
D
GERP RS
5.0
Varity_R
0.65

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: rs1553140066; hg19: chrM-9248; COSMIC: COSV62293170; COSMIC: COSV62293170; API