rs121434458

Positions:

• chrM-5591-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2 PP3 PP5_Very_Strong

The ENST00000387392.1(MT-TA):​n.65C>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: 𝑓 0.0 (AC: 0)
• Consequence: MT-TA ENST00000387392.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3 Myopathy
• Conservation: PhyloP100: 2.27

Genes affected

MT-TA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNA (HGNC:):

MT-TW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• PP5: Variant M-5591-G-A is Pathogenic according to our data. Variant chrM-5591-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNA	TRNA.1	n.65C>T		non_coding_transcript_exon_variant	1/1
TRNW	TRNW.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TA	ENST00000387392.1	n.65C>T		non_coding_transcript_exon_variant	1/1
MT-TW	ENST00000387382.1			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 GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56420

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56420

Mitomap

Myopathy

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

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.5591G>A variant in MT-TA 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, PM8, PM9, PP3, PP6 -

Inborn mitochondrial myopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 14, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Pathogenic	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434458; hg19: chrM-5592;