Genetic Variant COX1:p.Arg514Ile (chrM-7444-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Mitomap GenBank:

𝑓 0.0 ( AC: 0 )

Consequence

COX1
missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

No linked disesase in Mitomap

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

COX1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

COX1 links:

COX2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

COX2 links:

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

TRND links:

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank
COX1	unassigned_transcript_4799	c.1541G>T	p.Arg514Ile	missense_variant, splice_region_variant	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-142G>T		upstream_gene_variant
TRND	unassigned_transcript_4801	c.-74G>T		upstream_gene_variant
TRNS1	unassigned_transcript_4800	c.*2C>A		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:

0.0

AC:

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

GERP RS

-7.5

Varity_R

0.095

Splicing

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

Publications

No publications associated with this variant yet.