ENST00000361390.2:c.622G>A

Variant names:

• chrM-3928-G-A
• rs587776442
• ENST00000361390.2:c.622G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361390.2(MT-ND1):​c.622G>A​(p.Val208Ile) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V208L) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.35
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 7.57
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.35097668 < 0.5 .

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361390.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND1	ENST00000361390.2	TSL:6	c.622G>A	p.Val208Ile	missense	Exon 1 of 1	ENSP00000354687.2

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56428

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56428

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.35
Hmtvar	Benign	0.26
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.024	T
DEOGEN2	Benign	0.058	T
LIST_S2	Benign	0.85	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.6
PROVEAN	Benign	-0.95	N
Sift4G	Uncertain	0.0060	D
GERP RS		4.5
Varity_R		0.66
Mutation Taster		=40/60	disease causing

Other links and lift over

dbSNP: rs587776442; hg19: chrM-3929; COSMIC: COSV62294113; COSMIC: COSV62294113;