rs878853008

Variant names:

• chrM-4219-G-A
• rs878853008
• ENST00000361390.2:c.913G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361390.2(MT-ND1):​c.913G>A​(p.Val305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 49)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.018
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.0660
• Publications: 3 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)

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

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

TRNQ Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Apogee2 supports a benign effect, 0.017860007 < 0.5 .
• BP6: Variant M-4219-G-A is Benign according to our data. Variant chrM-4219-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 57

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.913G>A	p.Val305Ile	missense_variant	Exon 1 of 1
TRNI	unassigned_transcript_4790	c.-44G>A		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-183G>A		upstream_gene_variant
TRNQ	unassigned_transcript_4791	c.*110C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.913G>A	p.Val305Ile	missense_variant	Exon 1 of 1	6		ENSP00000354687.2
MT-TI	ENST00000387365.1	n.-44G>A		upstream_gene_variant		6
MT-TM	ENST00000387377.1	n.-183G>A		upstream_gene_variant		6
MT-TQ	ENST00000387372.1	n.*110C>T		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00080 AC: 49

Gnomad homoplasmic AF: 0.0010 AC: 57 AN: 56416

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56416

Alfa AF: 0.000897 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 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.4219G>A (YP_003024026.1:p.Val305Ile) variant in MTND1 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

not provided Benign:1

Aug 12, 2015

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
Apogee2	Benign	0.018
Hmtvar	Benign	0.080
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.59	T
DEOGEN2	Benign	0.0078	T
LIST_S2	Benign	0.54	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.066
PROVEAN	Benign	0.24	N
Sift4G	Benign	1.0	T
GERP RS		-2.0
Varity_R		0.29
Mutation Taster		=95/5	polymorphism

Other links and lift over

dbSNP: rs878853008; hg19: chrM-4220;