M-5913-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The ENST00000361624.2(MT-CO1):c.10G>A(p.Asp4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0089 (AC: 543)
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.023
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 Prostate-Cancer-/-hypertension
• Conservation: PhyloP100: 2.56

Genes affected

COX1 (HGNC:):

MT-CO1 (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]

MT-TY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.023371013 < 0.5 .
• BP6: Variant M-5913-G-A is Benign according to our data. Variant chrM-5913-G-A is described in ClinVar as [Benign]. Clinvar id is 692601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0089
• BS2: High AC in GnomadMitoHomoplasmic at 299

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX1	COX1.1	c.10G>A	p.Asp4Asn	missense_variant	1/1
TRNY	TRNY.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO1	ENST00000361624.2	c.10G>A	p.Asp4Asn	missense_variant	1/1			P1
MT-TY	ENST00000387409.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0089 AC: 543

Gnomad homoplasmic AF: 0.0053 AC: 299 AN: 56419

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56419

Alfa AF: 0.00441 Hom.: 36

Mitomap

Prostate-Cancer-/-hypertension

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 27, 2020

- -

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.5913G>A (YP_003024028.1:p.Asp4Asn) 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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.023
Hmtvar	Benign	0.050
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
DEOGEN2	Benign	0.0020	T
LIST_S2	Benign	0.65	T
MutationAssessor	Benign	-1.6	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.20	N
Sift4G	Benign	1.0	T
GERP RS		2.3
Varity_R		0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201617272; hg19: chrM-5914;