rs1603220128

Variant names:

• chrM-5802-T-C
• rs1603220128
• unassigned_transcript_4797:c.25A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The ENST00000000000(TRNC):​c.25A>G​(p.Asn9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: TRNC ENST00000000000 missense
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 DEAF1555-increased-penetrance-/-obesity-risk
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

Genes affected

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

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]

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

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

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

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

TRNY Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BS2: High AC in GnomadMitoHomoplasmic at 4

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387405.1. 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-TC	ENST00000387405.1	TSL:6	n.25A>G		non_coding_transcript_exon	Exon 1 of 1
	MT-CO1	ENST00000361624.2	TSL:6	c.-102T>C		upstream_gene	N/A	ENSP00000354499.2	P00395
	MT-TA	ENST00000387392.1	TSL:6	n.-147A>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

Disease(s): DEAF1555-increased-penetrance-/-obesity-risk

Status: Reported

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	13
Hmtvar	Benign	0.30
PhyloP100		2.2

Other links and lift over

dbSNP: rs1603220128; hg19: chrM-5803;