rs878853034

Variant names:

• chrM-4023-T-C
• rs878853034
• ENST00000361390.2:c.717T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361390.2(MT-ND1):​c.717T>C​(p.Thr239Thr) 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: 58)
• Consequence: MT-ND1 ENST00000361390.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -16.0
• Publications: 2 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]

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

TRNI Gene-Disease associations (from GenCC):

• mitochondrial disease

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

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant M-4023-T-C is Benign according to our data. Variant chrM-4023-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-16 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 45

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.717T>C	p.Thr239Thr	synonymous_variant	Exon 1 of 1
TRNI	unassigned_transcript_4790	c.-240T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.717T>C	p.Thr239Thr	synonymous_variant	Exon 1 of 1	6		ENSP00000354687.2
MT-TI	ENST00000387365.1	n.-240T>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00090 AC: 58

Gnomad homoplasmic AF: 0.00080 AC: 45 AN: 56429

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56429

Alfa AF: 0.000264 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 13, 2014

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		-16
Mutation Taster		=95/5	polymorphism

Other links and lift over

dbSNP: rs878853034; hg19: chrM-4024;