rs193303019

Variant names:

• chrM-3308-T-C
• rs28358582
• unassigned_transcript_4789:c.2T>C

Your query was ambiguous. Multiple possible variants found:

• chrM-3308-T-C
• chrM-3308-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.0070 (AC: 426)
• Consequence: ND1 missense
• Scores: Apogee2 Benign 0.33
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:2 B:3 MELAS-/-DEAF-enhancer-/-hypertension-/-LVNC-/-putative-LHON,Sudden-Infant-Death
• Conservation: PhyloP100: 4.72

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]

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant M-3308-T-C is Benign according to our data. Variant chrM-3308-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 9728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0069999998
• BS2: High AC in GnomadMitoHomoplasmic at 1609

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.2T>C	p.Ile1Thr	missense_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.*4T>C		downstream_gene_variant
RNR2	unassigned_transcript_4787	n.*79T>C		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: 0.0070 AC: 426

Gnomad homoplasmic AF: 0.029 AC: 1609 AN: 56409

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56409

Alfa AF: 0.0108 Hom.: 50

Mitomap

MELAS-/-DEAF-enhancer-/-hypertension-/-LVNC-/-putative-LHON,Sudden-Infant-Death

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:2 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 04, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 31, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Carcinoma of colon Pathogenic:1

Nov 01, 1999

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

SUDDEN INFANT DEATH SYNDROME Pathogenic:1

Nov 01, 1999

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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.3308T>C (YP_003024026.1:p.Met1Thr) 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.33
Hmtvar	Pathogenic	0.74
BayesDel_addAF	Benign	-0.23	T
GERP RS		3.1
Varity_R		0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28358582; hg19: chrM-3309; COSMIC: COSV104421140; COSMIC: COSV104421140;