rs199474661

Positions:

• chrM-3252-A-G
• chrM-3252-A-T

Variant summary

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

Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNL1 missense
• Scores: Mitotip Uncertain 11
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2 O:1 MELAS,EXIT
• Conservation: PhyloP100: 6.99

Genes affected

TRNL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-3252-A-G is Pathogenic according to our data. Variant chrM-3252-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9594.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNL1	unassigned_transcript_4789	c.23A>G	p.Asn8Ser	missense_variant	1/1
RNR2	unassigned_transcript_4788	n.*23A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

MELAS,EXIT

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Likely 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.3252A>G variant in MT-TL1 gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM8, PM9, PM10 -

Mitochondrial encephalomyopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 1993

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Pathogenic	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474661; hg19: chrM-3253;