rs118203887

chrM-622-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The ENST00000387314.1(MT-TF):n.46G>A variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TF ENST00000387314.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 12
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 EXIT-&-Deafness
• Conservation: PhyloP100: 5.21

Genes affected

MT-TF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

TRNF (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-622-G-A is Pathogenic according to our data. Variant chrM-622-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9575.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNF	TRNF.1	n.46G>A		non_coding_transcript_exon_variant	1/1
RNR1	RNR1.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TF	ENST00000387314.1	n.46G>A		non_coding_transcript_exon_variant	1/1
MT-RNR1	ENST00000389680.2			upstream_gene_variant

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: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56417

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56417

Mitomap

EXIT-&-Deafness

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Myopathy, mitochondrial, late-onset Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	12
Hmtvar	Pathogenic	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs118203887; hg19: chrM-624;