M-7534-C-T

Variant names:

• chrM-7534-C-T
• rs1603221002
• unassigned_transcript_4801:c.17C>T

Variant summary

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

The ENST00000000000(TRND):​c.17C>T​(p.Pro6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 11)
• Consequence: TRND ENST00000000000 missense
• Scores: Mitotip Benign 5.1
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -11.9
• Publications: 0 publications found

Genes affected

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-7534-C-T is Benign according to our data. Variant chrM-7534-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 690040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 5

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387419.1. 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-TD	ENST00000387419.1	TSL:6	n.17C>T		non_coding_transcript_exon	Exon 1 of 1
	MT-CO2	ENST00000361739.1	TSL:6	c.-52C>T		upstream_gene	N/A	ENSP00000354876.1	P00403
	MT-CO1	ENST00000361624.2	TSL:6	c.*89C>T		downstream_gene	N/A	ENSP00000354499.2	P00395

Frequencies

Mitomap GenBank AF: 0.00020 AC: 11

Gnomad homoplasmic AF: 0.000089 AC: 5 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely 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	Benign	5.1
Hmtvar	Benign	0.0
PhyloP100		-12

Other links and lift over

dbSNP: rs1603221002; hg19: chrM-7535;