rs118203890

Variant names:

• chrM-15950-G-A
• rs118203890
• unassigned_transcript_4819:c.63G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The ENST00000000000(TRNT):​c.63G>A​(p.Ter21Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNT ENST00000000000 stop_retained
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1 LHON-/-LHON-MS-/-dopaminergic-nerve-cell-death-(PD)-/-tic-disorder
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP Gene-Disease associations (from GenCC):

• MERRF syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT	unassigned_transcript_4819	c.63G>A	p.Ter21Ter	stop_retained_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.*63G>A		downstream_gene_variant
TRNP	unassigned_transcript_4820	c.*6C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TT	ENST00000387460.2	n.63G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CYB	ENST00000361789.2	c.*63G>A		downstream_gene_variant		6		ENSP00000354554.2
MT-TP	ENST00000387461.2	n.*6C>T		downstream_gene_variant		6

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56430

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56430

Alfa AF: 0.000341 Hom.: 4

Mitomap

Disease(s): LHON-/-LHON-MS-/-dopaminergic-nerve-cell-death-(PD)-/-tic-disorder

Status: Reported

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Uncertain:1

Jul 12, 2019

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15950G>A variant in MT-TT gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PP3, BP6 -

Parkinson disease, mitochondrial Other:1

Apr 01, 1999

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Benign	0.10
PhyloP100		1.5

Other links and lift over

dbSNP: rs118203890; hg19: chrM-15951;