rs1556424691

chrM-15923-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000387460.2(MT-TT):n.36A>G variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TT ENST00000387460.2 non_coding_transcript_exon
• Scores: Mitotip Uncertain 12
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:2 LIMM-/-MERRF-/-mito-disease
• Conservation: PhyloP100: 8.59

Genes affected

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

TRNT (HGNC:):

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-15923-A-G is Pathogenic according to our data. Variant chrM-15923-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 39575.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNT	TRNT.1	n.36A>G		non_coding_transcript_exon_variant	1/1
CYTB	CYTB.1			downstream_gene_variant
TRNP	TRNP.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TT	ENST00000387460.2	n.36A>G		non_coding_transcript_exon_variant	1/1
MT-CYB	ENST00000361789.2			downstream_gene_variant				P1
MT-TP	ENST00000387461.2			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 GenBank AF: 0.0 AC: 0

Alfa AF: 0.0572 Hom.: 470

Mitomap

LIMM-/-MERRF-/-mito-disease

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Undiagnosed Diseases Network, NIH

Mar 13, 2019

- -

Variant of unknown significance Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 01, 1992

- -

Constipation;C0022346:Jaundice;C0085298:Sudden cardiac death;C1848924:Infantile onset;C1855106:Neonatal onset;C1858120:Generalized hypotonia;C2315100:Failure to thrive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Sep 21, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	12
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: rs1556424691; hg19: chrM-15924;