rs878853040

Variant names:

• chrM-9467-T-C
• rs878853040
• ENST00000362079.2:c.261T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000362079.2(MT-CO3):​c.261T>C​(p.Ile87Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00050 (AC: 33)
• Consequence: MT-CO3 ENST00000362079.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.42
• Publications: 1 publications found

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-CO3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP6: Variant M-9467-T-C is Benign according to our data. Variant chrM-9467-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 235458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.42 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.261T>C	p.Ile87Ile	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.261T>C	p.Ile87Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000354982.2

Frequencies

Mitomap GenBank AF: 0.00050 AC: 33

Gnomad homoplasmic AF: 0.0014 AC: 78 AN: 56431

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56431

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 12, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.4
Mutation Taster		=77/23	polymorphism

Other links and lift over

dbSNP: rs878853040; hg19: chrM-9468;