M-5530-C-T

Variant names:

• chrM-5530-C-T
• rs1603220009
• unassigned_transcript_4794:c.19C>T

Variant summary

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

The ENST00000000000(TRNW):​c.19C>T​(p.Gln7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 27)
• Consequence: TRNW ENST00000000000 stop_gained
• Scores: Mitotip Benign 4.6
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

Genes affected

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNC Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant M-5530-C-T is Benign according to our data. Variant chrM-5530-C-T is described in ClinVar as Benign. ClinVar VariationId is 689928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 11

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387382.1. 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-TW	ENST00000387382.1	TSL:6	n.19C>T		non_coding_transcript_exon	Exon 1 of 1
	MT-ND2	ENST00000361453.3	TSL:6	c.*19C>T		downstream_gene	N/A	ENSP00000355046.4	P03891
	MT-TA	ENST00000387392.1	TSL:6	n.*57G>A		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00040 AC: 27

Gnomad homoplasmic AF: 0.00019 AC: 11 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

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	Benign	4.6
Hmtvar	Benign	0.10
PhyloP100		-1.5

Other links and lift over

dbSNP: rs1603220009; hg19: chrM-5531;