rs375986475

Variant names:

• chrM-4388-A-G
• rs375986475
• unassigned_transcript_4791:c.13T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The ENST00000000000(TRNQ):​c.13T>C​(p.Trp5Arg) variant causes a missense change. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0011 (AC: 67)
• Consequence: TRNQ ENST00000000000 missense
• Scores: Mitotip Benign -0.69
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1 Poss.-hypertension-factor|-intellectual-disability
• Conservation: PhyloP100: 5.82
• Publications: 1 publications found

Genes affected

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

TRNI Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant M-4388-A-G is Benign according to our data. Variant chrM-4388-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 235438.
• BS2: High AC in GnomadMitoHomoplasmic at 84

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387372.1. 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-TQ	ENST00000387372.1	TSL:6	n.13T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-ND2	ENST00000361453.3	TSL:6	c.-82A>G		upstream_gene	N/A	ENSP00000355046.4	P03891
	MT-ND1	ENST00000361390.2	TSL:6	c.*126A>G		downstream_gene	N/A	ENSP00000354687.2	P03886

Frequencies

Mitomap GenBank AF: 0.0011 AC: 67

Gnomad homoplasmic AF: 0.0015 AC: 84 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Alfa AF: 0.000727 Hom.: 0

Mitomap

Disease(s): Poss.-hypertension-factor|-intellectual-disability

Status: Reported

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	-0.69
Hmtvar	Benign	0.15
PhyloP100		5.8

Other links and lift over

dbSNP: rs375986475; hg19: chrM-4389;