M-4597-T-C

Position:

• chrM-4597-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361453.3(MT-ND2):​c.128T>C​(p.Val43Ala) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V43I) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.14
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.64

Genes affected

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.13735016 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.128T>C	p.Val43Ala	missense_variant	1/1			ENSP00000355046	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: 0.0 AC: 0

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Feb 18, 2018

The m. 4597T>C variant affects the MT-ND2 gene, which encodes a subunit of the mitochondrial complex I. Although this variant is not reported in the MITOMAP database, it also has not been associated with a mitochondrial disorder, and the nucleotide altered by this variant is weakly conserved (Alamut software v2.10.0). Due to limited information, the clinical significance of the m. 4597T>C variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.14
Hmtvar	Pathogenic	0.39
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.31	T
DEOGEN2	Benign	0.067	T
LIST_S2	Benign	0.70	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PROVEAN	Uncertain	-3.0	D
Sift4G	Pathogenic	0.0010	D
GERP RS		3.4
Varity_R		0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569483945; hg19: chrM-4598;