rs118203894

Variant names:

• chrM-5843-A-G
• rs118203894
• unassigned_transcript_4798:c.49T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The ENST00000000000(TRNY):​c.49T>C​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0074 (AC: 452)
• Consequence: TRNY ENST00000000000 synonymous
• Scores: Mitotip Benign 3.5
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 FSGS-/-Mitochondrial-Cytopathy
• Conservation: PhyloP100: 0.876
• Publications: 2 publications found

Genes affected

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

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)

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: Benign. The variant received -11 ACMG points.

• BP6: Variant M-5843-A-G is Benign according to our data. Variant chrM-5843-A-G is described in ClinVar as Benign. ClinVar VariationId is 9553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.876 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0074
• BS2: High AC in GnomadMitoHomoplasmic at 43

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNY	unassigned_transcript_4798	c.49T>C	p.Leu17Leu	synonymous_variant	Exon 1 of 1
COX1	unassigned_transcript_4799	c.-61A>G		upstream_gene_variant
TRNN	unassigned_transcript_4796	c.-114T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.-61A>G		upstream_gene_variant		6		ENSP00000354499.2

Frequencies

Mitomap GenBank AF: 0.0074 AC: 452

Gnomad homoplasmic AF: 0.00076 AC: 43 AN: 56422

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56422

Alfa AF: 0.000645 Hom.: 12

Mitomap

Disease(s): FSGS-/-Mitochondrial-Cytopathy

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis and dilated cardiomyopathy Pathogenic:1

Dec 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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.5843A>G variant in MT-TY 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: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.5
Hmtvar	Benign	0.30
PhyloP100		0.88

Other links and lift over

dbSNP: rs118203894; hg19: chrM-5844;