rs878853008

chrM-4219-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

MT-TI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

TRNI (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
TRNI	TRNI.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND1	ENST00000361390.2	c.913G>A	p.Val305Ile	missense_variant	1/1			P1
MT-TI	ENST00000387365.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

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

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

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

Likely benign, criteria provided, single submitter

clinical testing

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

Aug 12, 2015

- -

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
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.24	N
Sift4G	Benign	1.0	T
GERP RS		-2.0
Varity_R		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878853008; hg19: chrM-4220;