rs374875201

Variant names:

• chrM-3396-T-C
• rs374875201
• unassigned_transcript_4789:c.90T>C

Variant summary

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

Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0075 (AC: 459)
• Consequence: ND1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 NSHL-/-MIDD
• Conservation: PhyloP100: -3.93

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-3396-T-C is Benign according to our data. Variant chrM-3396-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0075
• BS2: High AC in GnomadMitoHomoplasmic at 851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.90T>C	p.Tyr30Tyr	synonymous_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.*92T>C		downstream_gene_variant
RNR2	unassigned_transcript_4787	n.*167T>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: 0.0075 AC: 459

Gnomad homoplasmic AF: 0.015 AC: 851 AN: 56421

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56421

Alfa AF: 0.00406 Hom.: 34

Mitomap

NSHL-/-MIDD

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 18, 2016

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374875201; hg19: chrM-3397; COSMIC: COSV62293147; COSMIC: COSV62293147;