dbSNP rs199474672: TRNW:p.Lys9fs (chrM-5537-A-AT) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The ENST00000000000(TRNW):c.26_27insT(p.Lys9fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Mitomap GenBank:

Absent

Consequence

TRNW
ENST00000000000 frameshift

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:3O:1

Leigh-Syndrome

Conservation

PhyloP100: 0.787

Publications

1 publications found

Variant links:

Genes affected

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNW links:

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND2 links:

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNN links:

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNA links:

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNC Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

TRNC links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000000000, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

No frequency data in Mitomap. Probably very rare.

PP5

Variant M-5537-A-AT is Pathogenic according to our data. Variant chrM-5537-A-AT is described in ClinVar as Pathogenic. ClinVar VariationId is 9555.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387382.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MT-TW	ENST00000387382.1	TSL:6	n.26_27insT	non_coding_transcript_exon	Exon 1 of 1
MT-ND2	ENST00000361453.3	TSL:6	c.26_27insT	downstream_gene	N/A	ENSP00000355046.4	P03891
MT-TA	ENST00000387392.1	TSL:6	n.49_50insA	downstream_gene	N/A

Frequencies

Mitomap GenBank

The variant is not present, suggesting it is rare.

Mitomap

Disease(s): Leigh-Syndrome

Status: Cfrm-[LP]

Publication(s):

9266739

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Leigh syndrome (2)

Mitochondrial encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.79

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Mitomap

ClinVar

Computational scores

Publications

Other links and lift over