rs878853008

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Mitomap GenBank:
𝑓 0.00080 ( AC: 49 )

Consequence

ND1
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
Variant links:
Genes affected
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

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 rank MANE Protein UniProt
ND1unassigned_transcript_4789 c.913G>A p.Val305Ile missense_variant Exon 1 of 1
TRNIunassigned_transcript_4790 c.-44G>A upstream_gene_variant
TRNMunassigned_transcript_4792 c.-183G>A upstream_gene_variant
TRNQunassigned_transcript_4791 c.*110C>T downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

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
LINK: link

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
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs878853008; hg19: chrM-4220; API