M-3498-C-T

Variant names:

• chrM-3498-C-T
• rs878982719
• ENST00000361390.2:c.192C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The ENST00000361390.2(MT-ND1):​c.192C>T​(p.Ala64Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 55)
• Consequence: MT-ND1 ENST00000361390.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -4.87
• Publications: 0 publications found

Genes affected

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]

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

TRNL1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE, LIMITED Submitted by: G2P, ClinGen
• maternally-inherited diabetes and deafness

  Inheritance: Mitochondrial Classification: STRONG Submitted by: Genomics England PanelApp
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP6: Variant M-3498-C-T is Benign according to our data. Variant chrM-3498-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 377309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.87 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 11

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361390.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND1	ENST00000361390.2	TSL:6	c.192C>T	p.Ala64Ala	synonymous	Exon 1 of 1	ENSP00000354687.2
	MT-TL1	ENST00000386347.1	TSL:6	n.*194C>T		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00090 AC: 55

Gnomad homoplasmic AF: 0.00019 AC: 11 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.000223 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 06, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.9
Mutation Taster		=90/10	polymorphism

Other links and lift over

dbSNP: rs878982719; hg19: chrM-3499;