M-9311-T-TGCA

Position:

• chrM-9311-T-TGCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The ENST00000362079.2(MT-CO3):​c.105_106insGCA​(p.Phe35_His36insAla) variant causes a inframe insertion change. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-CO3 ENST00000362079.2 inframe_insertion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.80

Genes affected

COX3 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PM4: Nonframeshift variant in NON repetitive region in ENST00000362079.2. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant M-9311-T-TGCA is Pathogenic according to our data. Variant chrM-9311-T-TGCA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 590894.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX3	COX3.1	c.105_106insGCA	p.Phe35_His36insAla	inframe_insertion	1/1		YP_003024032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.105_106insGCA	p.Phe35_His36insAla	inframe_insertion	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

No disease associated.

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Abnormal aortic valve physiology Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Molecular Biology Laboratory, University of Basrah

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569484292; hg19: chrM-9312;