rs199474701

chrM-15967-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The ENST00000387461.2(MT-TP):n.57C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TP ENST00000387461.2 non_coding_transcript_exon
• Scores: Mitotip Pathogenic 17
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 MERRF-like-disease
• Conservation: PhyloP100: -1.86

Genes affected

MT-TP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP (HGNC:):

MT-TT (HGNC:7499): (mitochondrially encoded tRNA threonine)

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• PP5: Variant M-15967-G-A is Pathogenic according to our data. Variant chrM-15967-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9572.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNP	TRNP.1	n.57C>T		non_coding_transcript_exon_variant	1/1
TRNT	TRNT.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TP	ENST00000387461.2	n.57C>T		non_coding_transcript_exon_variant	1/1
MT-TT	ENST00000387460.2			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

MERRF-like-disease

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

MERFF syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2009

- -

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

Pathogenic, 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.15967G>A variant in MT-TP gene is interpreted to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS3, PM7, PM8, PM9 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Pathogenic	17
Hmtvar	Pathogenic	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474701; hg19: chrM-15968;