M-15908-T-C

Variant names:

• chrM-15908-T-C
• rs386829266
• unassigned_transcript_4819:c.21T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNT):​c.21T>C​(p.Asn7Asn) variant causes a synonymous change. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0032 (AC: 197)
• Consequence: TRNT ENST00000000000 synonymous
• Scores: Mitotip Uncertain 9.2
• Clinical Significance: Benign criteria provided, single submitter B:1 DEAF-helper-mutation
• Conservation: PhyloP100: 6.36
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-15908-T-C is Benign according to our data. Variant chrM-15908-T-C is described in ClinVar as Benign. ClinVar VariationId is 690227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 53

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TT	ENST00000387460.2	TSL:6	n.21T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-CYB	ENST00000361789.2	TSL:6	c.*21T>C		downstream_gene	N/A	ENSP00000354554.2	P00156
	MT-TP	ENST00000387461.2	TSL:6	n.*48A>G		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0032 AC: 197

Gnomad homoplasmic AF: 0.00094 AC: 53 AN: 56418

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56418

Alfa AF: 0.000334 Hom.: 0

Mitomap

Disease(s): DEAF-helper-mutation

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	9.2
Hmtvar	Benign	0.25
PhyloP100		6.4

Other links and lift over

dbSNP: rs386829266; hg19: chrM-15909;