rs878853103

Variant names:

• chrM-11560-A-G
• rs878853103
• ENST00000361381.2:c.801A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The ENST00000361381.2(MT-ND4):​c.801A>G​(p.Trp267Trp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0014 (AC: 88)
• 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: 0.638
• Publications: 3 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 -13 ACMG points.

• BP6: Variant M-11560-A-G is Benign according to our data. Variant chrM-11560-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.638 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 97

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.801A>G	p.Trp267Trp	synonymous	Exon 1 of 1	ENSP00000354961.2	P03905

Frequencies

Mitomap GenBank AF: 0.0014 AC: 88

Gnomad homoplasmic AF: 0.0017 AC: 97 AN: 56426

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56426

Alfa AF: 0.00123 Hom.: 13

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
PhyloP100		0.64
GERP RS		2.0

Other links and lift over

dbSNP: rs878853103; hg19: chrM-11561;