rs374875201

Positions:

• chrM-3396-T-C

Variant summary

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

The ENST00000361390.2(MT-ND1):​c.90T>C​(p.Tyr30=) 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

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]

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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.90T>C	p.Tyr30=	synonymous_variant	1/1			ENSP00000354687	P1

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 18, 2016	- -

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;