ENST00000361381.2:c.39A>G

Variant names:

• chrM-10798-A-G
• rs1556423866
• ENST00000361381.2:c.39A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP6_Moderate BP7

The ENST00000361381.2(MT-ND4):​c.39A>G​(p.Pro13Pro) 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 0.00010 (AC: 7)
• Consequence: MT-ND4 ENST00000361381.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -12.4
• Publications: 0 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]

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4L Gene-Disease associations (from GenCC):

• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP6: Variant M-10798-A-G is Benign according to our data. Variant chrM-10798-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 445798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-12.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4	unassigned_transcript_4811	c.39A>G	p.Pro13Pro	synonymous_variant	Exon 1 of 1
ND4L	unassigned_transcript_4810	c.*32A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND4	ENST00000361381.2	c.39A>G	p.Pro13Pro	synonymous_variant	Exon 1 of 1	6		ENSP00000354961.2
MT-ND4L	ENST00000361335.1	c.*32A>G		downstream_gene_variant		6		ENSP00000354728.1

Frequencies

Mitomap GenBank AF: 0.00010 AC: 7

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56430

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56430

Alfa AF: 0.000111 Hom.: 0

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 08, 2017

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		-12
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs1556423866; hg19: chrM-10799;