M-10454-T-C

Position:

• chrM-10454-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000387439.1(MT-TR):​n.50T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0037 (AC: 229)
• Consequence: MT-TR ENST00000387439.1 non_coding_transcript_exon
• Scores: Mitotip Benign 2.7
• Clinical Significance: Benign criteria provided, single submitter B:1 Possible-deafness-or-maternally-inherited-hypertension-risk-factor
• Conservation: PhyloP100: -0.378

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 Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-10454-T-C is Benign according to our data. Variant chrM-10454-T-C is described in ClinVar as [Benign]. Clinvar id is 690122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 225

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNR	TRNR.1	n.50T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TR	ENST00000387439.1	n.50T>C		non_coding_transcript_exon_variant	1/1
MT-ND4L	ENST00000361335.1			upstream_gene_variant				P1
MT-ND3	ENST00000361227.2			downstream_gene_variant				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: 0.0037 AC: 229

Gnomad homoplasmic AF: 0.0040 AC: 225 AN: 56429

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56429

Alfa AF: 0.00201 Hom.: 9

Mitomap

Possible-deafness-or-maternally-inherited-hypertension-risk-factor

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.10454T>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, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.7
Hmtvar	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs878874133; hg19: chrM-10455;