M-10440-T-C

Position:

• chrM-10440-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000387439.1(MT-TR):​n.36T>C variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: MT-TR ENST00000387439.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.82

Genes affected

MT-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR (HGNC:):

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP6: Variant M-10440-T-C is Benign according to our data. Variant chrM-10440-T-C is described in ClinVar as [Benign]. Clinvar id is 690119.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNR	TRNR.1	n.36T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TR	ENST00000387439.1	n.36T>C		non_coding_transcript_exon_variant	1/1
MT-ND4L	ENST00000361335.1			upstream_gene_variant				ENSP00000354728	P1
MT-ND3	ENST00000361227.2			downstream_gene_variant				ENSP00000355206	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: 0.0 AC: 1

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56420

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56420

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1

Benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Jul 12, 2019

The NC_012920.1:m.10440T>C variant in MT-TR gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Benign	0.050

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603222833; hg19: chrM-10441;