rs3134560

Variant names:

• chrM-12192-G-A
• rs3134560
• unassigned_transcript_4812:c.55G>A

Your query was ambiguous. Multiple possible variants found:

• chrM-12192-G-A
• chrM-12192-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNH):​c.55G>A​(p.Asp19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0021 (AC: 126)
• Consequence: TRNH ENST00000000000 missense
• Scores: Mitotip Benign 2.7
• Clinical Significance: Benign criteria provided, single submitter P:2 B:1 MICM-/-possible-G15927A-deafness-modulator
• Conservation: PhyloP100: -4.60
• Publications: 6 publications found

Genes affected

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) 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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-12192-G-A is Benign according to our data. Variant chrM-12192-G-A is described in ClinVar as Benign. ClinVar VariationId is 9608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 223

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNH	unassigned_transcript_4812	c.55G>A	p.Asp19Asn	missense_variant	Exon 1 of 1
ND5	unassigned_transcript_4815	c.-145G>A		upstream_gene_variant
TRNL2	unassigned_transcript_4814	c.-74G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.-145G>A		upstream_gene_variant		6		ENSP00000354813.2
MT-ND4	ENST00000361381.2	c.*55G>A		downstream_gene_variant		6		ENSP00000354961.2

Frequencies

Mitomap GenBank AF: 0.0021 AC: 126

Gnomad homoplasmic AF: 0.0040 AC: 223 AN: 56428

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56428

Alfa AF: 0.00286 Hom.: 52

Mitomap

Disease(s): MICM-/-possible-G15927A-deafness-modulator

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Pathogenic:2 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CARDIOMYOPATHY, HYPERTROPHIC, MITOCHONDRIAL Pathogenic:1

Jan 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

CARDIOMYOPATHY, IDIOPATHIC DILATED, MITOCHONDRIAL Pathogenic:1

Jan 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

MELAS syndrome Benign:1

Jul 12, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.12192G>A variant in MT-TH gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.7
Hmtvar	Benign	0.20
PhyloP100		-4.6

Other links and lift over

dbSNP: rs3134560; hg19: chrM-12193;