M-5911-C-T

Position:

• chrM-5911-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0042 (AC: 259)
• Consequence: COX1 missense
• Scores: Apogee2 Benign 0.031
• Clinical Significance: Benign criteria provided, single submitter B:1 Prostate-Cancer
• Conservation: PhyloP100: 1.90

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]

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-5911-C-T is Benign according to our data. Variant chrM-5911-C-T is described in ClinVar as [Benign]. Clinvar id is 692600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 196

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.8C>T	p.Ala3Val	missense_variant	1/1
TRNY	unassigned_transcript_4798	c.-20G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0042 AC: 259

Gnomad homoplasmic AF: 0.0035 AC: 196 AN: 56432

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56432

Alfa AF: 0.000224 Hom.: 1

Mitomap

Prostate-Cancer

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.5911C>T (YP_003024028.1:p.Ala3Val) variant in MTCO1 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.031
Hmtvar	Benign	0.070
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.45	T
DEOGEN2	Benign	0.0020	T
LIST_S2	Benign	0.72	T
MutationAssessor	Benign	-1.1	N
PROVEAN	Benign	0.15	N
Sift4G	Benign	0.25	T
GERP RS		3.2
Varity_R		0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879227822; hg19: chrM-5912;