M-3391-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361390.2(MT-ND1):c.85G>A(p.Gly29Ser) variant causes a missense change. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 54)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Uncertain 0.41
• Clinical Significance: Benign criteria provided, single submitter B:1 LHON
• Conservation: PhyloP100: 6.25

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 -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.405958 < 0.5 .
• BP6: Variant M-3391-G-A is Benign according to our data. Variant chrM-3391-G-A is described in ClinVar as [Benign]. Clinvar id is 692348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 19

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.85G>A	p.Gly29Ser	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: 0.00090 AC: 54

Gnomad homoplasmic AF: 0.00034 AC: 19 AN: 56425

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56425

Alfa AF: 0.000445 Hom.: 2

Mitomap

LHON

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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.3391G>A (YP_003024026.1:p.Gly29Ser) 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Uncertain	0.41
Hmtvar	Pathogenic	0.87
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.15	T
DEOGEN2	Benign	0.13	T
LIST_S2	Benign	0.80	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-4.9	D
Sift4G	Benign	0.10	T
GERP RS		4.5
Varity_R		0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603218931; hg19: chrM-3392;