rs199476144

Positions:

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong

The ENST00000387342.1(MT-TV):​n.23C>T variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 0 )

Consequence

MT-TV
ENST00000387342.1 non_coding_transcript_exon

Scores

Mitotip
Uncertain
15

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:3O:1
Leigh-Syndrome

Conservation

PhyloP100: 5.78
Variant links:
Genes affected
MT-TV (HGNC:7500): (mitochondrially encoded tRNA valine)
MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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-1624-C-T is Pathogenic according to our data. Variant chrM-1624-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRNVTRNV.1 use as main transcriptn.23C>T non_coding_transcript_exon_variant 1/1
RNR2RNR2.1 use as main transcript upstream_gene_variant
RNR1RNR1.1 use as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MT-TVENST00000387342.1 linkuse as main transcriptn.23C>T non_coding_transcript_exon_variant 1/1
MT-RNR2ENST00000387347.2 linkuse as main transcript upstream_gene_variant
MT-RNR1ENST00000389680.2 linkuse as main transcript 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:
56433
Gnomad heteroplasmic
AF:
0.000018
AC:
1
AN:
56433

Mitomap

Leigh-Syndrome

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Pathogenic:2
Likely pathogenic, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineJul 12, 2019The NC_012920.1:m.1624C>T variant in MT-TV 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: PS3, PP3, PP4 -
Pathogenic, criteria provided, single submitterclinical testingMendelicsMay 04, 2022- -
Leigh syndrome, mitochondrial Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMFeb 01, 2002- -
Leigh syndrome Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mitotip
Uncertain
15
Hmtvar
Pathogenic
0.45

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199476144; hg19: chrM-1626; API