rs28357970

Positions:

• chrM-3796-A-G
• chrM-3796-A-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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:2 Adult-Onset-Dystonia
• Conservation: PhyloP100: 0.320

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 9730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 466

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND1	ENST00000361390.2	c.490A>G	p.Thr164Ala	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

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

Adult-Onset-Dystonia

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dystonia, adult-onset Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2003

- -

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.3796A>G (YP_003024026.1:p.Thr164Ala) variant in MTND1 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	2.2e-10	A
PROVEAN	Uncertain	-3.3	D
Sift4G	Benign	0.066	T
GERP RS		-6.8
Varity_R		0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28357970; hg19: chrM-3797;