dbSNP rs28380140: COX3:p.Ter57Trpext*? (chrM-9377-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Mitomap GenBank:

𝑓 0.0084 ( AC: 511 )

Consequence

COX3
stop_lost

Scores

Clinical Significance

Not reported in ClinVar

No linked disesase in Mitomap

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

COX3 (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]

COX3 links:

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]

ATP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

High frequency in mitomap database: 0.0084

BS2

High AC in GnomadMitoHomoplasmic at 493

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.171A>G	p.Ter57Trpext*?	stop_lost	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.*170A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome

Cov.:

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank

AF:

0.0084

AC:

511

Gnomad homoplasmic

AF:

0.0087

AC:

493

AN:

56361

Gnomad heteroplasmic

AF:

0.000071

AC:

AN:

56361

Alfa

AF:

0.00352

Hom.:

131

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.