rs387907318

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT	unassigned_transcript_4819	c.37A>G	p.Thr13Ala	missense_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.*37A>G		downstream_gene_variant
TRNP	unassigned_transcript_4820	c.*32T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TT	ENST00000387460.2	n.37A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CYB	ENST00000361789.2	c.*37A>G		downstream_gene_variant		6		ENSP00000354554.2
MT-TP	ENST00000387461.2	n.*32T>C		downstream_gene_variant		6

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 v4.3

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;