rs28718242

Variant names:

• chrM-11899-T-C
• rs28718242
• ENST00000361381.2:c.1140T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000361381.2(MT-ND4):​c.1140T>C​(p.Ser380Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0086 (AC: 528)
• Consequence: MT-ND4 ENST00000361381.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -8.87
• Publications: 4 publications found

Genes affected

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) 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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

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

TRNH 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: Benign. The variant received -17 ACMG points.

• BP6: Variant M-11899-T-C is Benign according to our data. Variant chrM-11899-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.87 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0086
• BS2: High AC in GnomadMitoHomoplasmic at 585

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4	unassigned_transcript_4811	c.1140T>C	p.Ser380Ser	synonymous_variant	Exon 1 of 1
TRNH	unassigned_transcript_4812	c.-239T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND4	ENST00000361381.2	c.1140T>C	p.Ser380Ser	synonymous_variant	Exon 1 of 1	6		ENSP00000354961.2
MT-TH	ENST00000387441.1	n.-239T>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0086 AC: 528

Gnomad homoplasmic AF: 0.010 AC: 585 AN: 56425

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56425

Alfa AF: 0.00671 Hom.: 295

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 12, 2015

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-8.9
Mutation Taster		=96/4	polymorphism

Other links and lift over

dbSNP: rs28718242; hg19: chrM-11900;