M-15889-T-C

Position:

• chrM-15889-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 48)
• Consequence: TRNT missense
• Scores: Mitotip Benign 7.7
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.114

Genes affected

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

CYTB (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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-15889-T-C is Benign according to our data. Variant chrM-15889-T-C is described in ClinVar as [Benign]. Clinvar id is 690213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 108

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNT	unassigned_transcript_4819	c.2T>C	p.Val1Ala	missense_variant	1/1
CYTB	unassigned_transcript_4818	c.*2T>C		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 GenBank AF: 0.00080 AC: 48

Gnomad homoplasmic AF: 0.0019 AC: 108 AN: 56424

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56424

Alfa AF: 0.000292 Hom.: 11

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Benign:1

Benign, 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.15889T>C variant in MT-TT gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	7.7
Hmtvar	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199833246; hg19: chrM-15890;