rs374875201

Variant names:

• chrM-3396-T-C
• rs374875201
• ENST00000361390.2:c.90T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000361390.2(MT-ND1):​c.90T>C​(p.Tyr30Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0075 (AC: 459)
• Consequence: MT-ND1 ENST00000361390.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 NSHL-/-MIDD
• Conservation: PhyloP100: -3.93
• Publications: 7 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]

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

MT-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]

MT-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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
MT-ND1	ENST00000361390.2	c.90T>C	p.Tyr30Tyr	synonymous_variant	Exon 1 of 1	6		ENSP00000354687.2
MT-TL1	ENST00000386347.1	n.*92T>C		downstream_gene_variant		6
MT-RNR2	ENST00000387347.2	n.*167T>C		downstream_gene_variant		6

Frequencies

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: 0.0233 Hom.: 349

Mitomap

Disease(s): NSHL-/-MIDD

Status: Reported-/-Unclear

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.9
Mutation Taster		=68/32	polymorphism

Other links and lift over

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