rs28357970

Variant names:

• chrM-3796-A-G
• rs28357970
• ENST00000361390.2:c.490A>G
• MT-ND1 p.Thr164Ala

Your query was ambiguous. Multiple possible variants found:

• chrM-3796-A-G
• chrM-3796-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361390.2(MT-ND1):​c.490A>G​(p.Thr164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T164S) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0047 (AC: 289)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.069
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:4 Adult-Onset-Dystonia
• Conservation: PhyloP100: 0.320
• Publications: 26 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: G2P, Orphanet
• 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 -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.068721496 < 0.5 .
• BP6: Variant M-3796-A-G is Benign according to our data. Variant chrM-3796-A-G is described in ClinVar as Benign. ClinVar VariationId is 9730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 466

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

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-ND1	ENST00000361390.2	TSL:6	c.490A>G	p.Thr164Ala	missense	Exon 1 of 1	ENSP00000354687.2	P03886

Frequencies

Mitomap GenBank AF: 0.0047 AC: 289

Gnomad homoplasmic AF: 0.0083 AC: 466 AN: 56424

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56424

Alfa AF: 0.00837 Hom.: 68

Mitomap

Disease(s): Adult-Onset-Dystonia

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
1	-	-	Dystonia, adult-onset (1)
-	-	1	Leigh syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.069
Hmtvar	Benign	0.13
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.46	T
DEOGEN2	Benign	0.096	T
LIST_S2	Benign	0.32	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.32
PROVEAN	Uncertain	-3.3	D
Sift4G	Benign	0.066	T
Varity_R		0.46
Mutation Taster		=92/8	polymorphism

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28357970;

hg19: chrM-3797;