M-15924-A-G

Variant names:

• chrM-15924-A-G
• rs193303001
• unassigned_transcript_4819:c.37A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000000000(TRNT):​c.37A>G​(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.035 (AC: 2140)
• Consequence: TRNT ENST00000000000 missense
• Scores: Mitotip Benign 8.0
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 LIMM
• Conservation: PhyloP100: -0.408
• Publications: 4 publications found

Genes affected

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

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]

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP Gene-Disease associations (from GenCC):

• MERRF syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant M-15924-A-G is Benign according to our data. Variant chrM-15924-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 690236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.035

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387460.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TT	ENST00000387460.2	TSL:6	n.37A>G		non_coding_transcript_exon	Exon 1 of 1
	MT-CYB	ENST00000361789.2	TSL:6	c.*37A>G		downstream_gene	N/A	ENSP00000354554.2
	MT-TP	ENST00000387461.2	TSL:6	n.*32T>C		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.035 AC: 2140

Gnomad homoplasmic AF: 0.041 AC: 2316 AN: 56287

Gnomad heteroplasmic AF: 0.00052 AC: 29 AN: 56287

Alfa AF: 0.0636 Hom.: 1265

Mitomap

Disease(s): LIMM

Status: Reported

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15924A>G 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: BA1, BP4

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	8.0
Hmtvar	Pathogenic	0.40
PhyloP100		-0.41
Mutation Taster		=96/4	polymorphism

Other links and lift over

dbSNP: rs193303001; hg19: chrM-15925;