rs28357968

Variant names:

• chrM-3666-G-A
• rs28357968
• ENST00000361390.2:c.360G>A

Your query was ambiguous. Multiple possible variants found:

• chrM-3666-G-A
• chrM-3666-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The ENST00000361390.2(MT-ND1):​c.360G>A​(p.Gly120Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.021 (AC: 1267)
• Consequence: MT-ND1 ENST00000361390.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -5.55
• Publications: 9 publications found

Genes affected

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND1 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
• mitochondrial complex I deficiency

  Inheritance: AR 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-5.55 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0207

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND1	unassigned_transcript_4789	c.360G>A	p.Gly120Gly	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND1	ENST00000361390.2	c.360G>A	p.Gly120Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000354687.2

Frequencies

Mitomap GenBank AF: 0.021 AC: 1267

Gnomad homoplasmic AF: 0.054 AC: 3045 AN: 56399

Gnomad heteroplasmic AF: 0.00020 AC: 11 AN: 56399

Alfa AF: 0.0325 Hom.: 1572

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.6
Mutation Taster		=51/149	disease causing

Other links and lift over

dbSNP: rs28357968; hg19: chrM-3667; COSMIC: COSV104421142; COSMIC: COSV104421142;