rs200873900

Variant names:

• chrM-11696-G-A
• rs200873900
• ENST00000361381.2:c.937G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The ENST00000361381.2(MT-ND4):​c.937G>A​(p.Val313Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0060 (AC: 365)
• Consequence: MT-ND4 ENST00000361381.2 missense
• Scores: Apogee2 Benign 0.34
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 LHON-/-LDYT-/-DEAF-/-hypertension-helper-mut.
• Conservation: PhyloP100: 1.12
• Publications: 16 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-ND4 Gene-Disease associations (from GenCC):

• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leber plus disease

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.33835188 < 0.5 .
• BP6: Variant M-11696-G-A is Benign according to our data. Variant chrM-11696-G-A is described in ClinVar as Benign. ClinVar VariationId is 9710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.006
• BS2: High AC in GnomadMitoHomoplasmic at 56

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361381.2. 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-ND4	ENST00000361381.2	TSL:6	c.937G>A	p.Val313Ile	missense	Exon 1 of 1	ENSP00000354961.2	P03905

Frequencies

Mitomap GenBank AF: 0.0060 AC: 365

Gnomad homoplasmic AF: 0.00099 AC: 56 AN: 56427

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56427

Alfa AF: 0.00108 Hom.: 50

Mitomap

Disease(s): LHON-/-LDYT-/-DEAF-/-hypertension-helper-mut.

Status: Reported-/-possibly-synergistic

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Leber optic atrophy and dystonia (1)
-	-	1	Leigh syndrome (1)
-	-	-	Leber optic atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.34
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.45	T
DEOGEN2	Benign	0.013	T
LIST_S2	Benign	0.29	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.1
PROVEAN	Benign	-0.32	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
GERP RS		0.49
Varity_R		0.13
Mutation Taster		=96/4	polymorphism

Other links and lift over

dbSNP: rs200873900; hg19: chrM-11697;