rs878853046

Variant names:

• chrM-12432-C-T
• rs878853046
• ENST00000361567.2:c.96C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361567.2(MT-ND5):​c.96C>T​(p.Tyr32Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0015 (AC: 94)
• Consequence: MT-ND5 ENST00000361567.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -5.92
• Publications: 0 publications found

Genes affected

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-5.92 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 23

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.96C>T	p.Tyr32Tyr	synonymous_variant	Exon 1 of 1
TRNL2	unassigned_transcript_4814	c.*96C>T		downstream_gene_variant
TRNH	unassigned_transcript_4812	c.*226C>T		downstream_gene_variant
TRNS2	unassigned_transcript_4813	c.*167C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.96C>T	p.Tyr32Tyr	synonymous_variant	Exon 1 of 1	6		ENSP00000354813.2
MT-TH	ENST00000387441.1	n.*226C>T		downstream_gene_variant		6
MT-TS2	ENST00000387449.1	n.*167C>T		downstream_gene_variant		6
MT-TL2	ENST00000387456.1	n.*96C>T		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0015 AC: 94

Gnomad homoplasmic AF: 0.00041 AC: 23 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 22, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.9
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs878853046; hg19: chrM-12433;