M-616-T-G

Variant names:

• chrM-616-T-G
• rs387906420
• unassigned_transcript_4784:c.40T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000000000(TRNF):​c.40T>G​(p.Cys14Gly) variant causes a missense change. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: TRNF ENST00000000000 missense
• Scores: Mitotip Pathogenic 20
• Clinical Significance: Pathogenic no assertion criteria provided P:1 Maternally-inherited-epilepsy-/-mito-tubulointerstitial-kidney-disease-(MITKD)-/-Gitelman-like-syndrome,Maternally-inherited-epilepsy
• Conservation: PhyloP100: 3.71
• Publications: 1 publications found

Genes affected

TRNF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-616-T-G is Pathogenic according to our data. Variant chrM-616-T-G is described in ClinVar as Pathogenic. ClinVar VariationId is 9577.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387314.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TF	ENST00000387314.1	TSL:6	n.40T>G		non_coding_transcript_exon	Exon 1 of 1
	MT-RNR1	ENST00000389680.2	TSL:6	n.-32T>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 1

Mitomap

Disease(s): Maternally-inherited-epilepsy-/-mito-tubulointerstitial-kidney-disease-(MITKD)-/-Gitelman-like-syndrome,Maternally-inherited-epilepsy

Status: Cfrm-[LP],Reported

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Epilepsy, mitochondrial Pathogenic:1

Feb 09, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Pathogenic	20
Hmtvar	Benign	0.25
PhyloP100		3.7

Other links and lift over

dbSNP: rs387906420; hg19: chrM-618;