rs878853023

Variant names:

• chrM-6120-A-G
• rs878853023
• ENST00000361624.2:c.217A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000361624.2(MT-CO1):​c.217A>G​(p.Ile73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I73T) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.018
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 3.30
• Publications: 1 publications found

Genes affected

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]

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

TRNY Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.018204905 < 0.5 .
• BS2: High AC in GnomadMitoHomoplasmic at 10

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361624.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO1	ENST00000361624.2	TSL:6	c.217A>G	p.Ile73Val	missense	Exon 1 of 1	ENSP00000354499.2	P00395
	MT-TY	ENST00000387409.1	TSL:6	n.-229T>C		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00010 AC: 9

Gnomad homoplasmic AF: 0.00018 AC: 10 AN: 56428

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56428

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Leigh syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.018
Hmtvar	Pathogenic	0.61
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.37	T
DEOGEN2	Benign	0.015	T
LIST_S2	Benign	0.82	T
MutationAssessor	Benign	0.56	N
PhyloP100		3.3
PROVEAN	Benign	-0.50	N
Sift4G	Benign	0.19	T
GERP RS		5.1
Varity_R		0.63
Mutation Taster		=59/41	polymorphism

Other links and lift over

dbSNP: rs878853023; hg19: chrM-6121;