M-7674-T-C

Variant names:

• chrM-7674-T-C
• rs1569484168
• ENST00000361739.1:c.89T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361739.1(MT-CO2):​c.89T>C​(p.Ile30Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I30V) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 16)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.16
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 3.98
• Publications: 0 publications found

Genes affected

MT-CO2 (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]

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]

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

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

TRND Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.15822265 < 0.5 .
• BP6: Variant M-7674-T-C is Benign according to our data. Variant chrM-7674-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 692758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 18

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361739.1. 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-CO2	ENST00000361739.1	TSL:6	c.89T>C	p.Ile30Thr	missense	Exon 1 of 1	ENSP00000354876.1	P00403
	MT-CO1	ENST00000361624.2	TSL:6	c.*229T>C		downstream_gene	N/A	ENSP00000354499.2	P00395
	MT-TS1	ENST00000387416.2	TSL:6	n.-160A>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00030 AC: 16

Gnomad homoplasmic AF: 0.00032 AC: 18 AN: 56427

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56427

Alfa AF: 0.000669 Hom.: 2

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.16
Hmtvar	Benign	0.24
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.23	T
DEOGEN2	Benign	0.15	T
LIST_S2	Benign	0.70	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.0
PROVEAN	Uncertain	-3.5	D
Sift	Benign	0.038	D
Sift4G	Uncertain	0.022	D
GERP RS		4.3
Varity_R		0.21

Other links and lift over

dbSNP: rs1569484168; hg19: chrM-7675;