chrM-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 CliVar as Likely_benign. Clinvar id is 377309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrM-3498-C-T is described in CliVar as Likely_benign. Clinvar id is 377309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrM-3498-C-T is described in CliVar as Likely_benign. Clinvar id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.192C>T	p.Ala64Ala	synonymous_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.*194C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.192C>T	p.Ala64Ala	synonymous_variant	Exon 1 of 1	6		ENSP00000354687.2
MT-TL1	ENST00000386347.1	n.*194C>T		downstream_gene_variant		6

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs878982719; hg19: chrM-3499;