M-4561-T-C

Position:

• chrM-4561-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The ENST00000361453.3(MT-ND2):​c.92T>C​(p.Val31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0063 (AC: 386)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.050
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.651

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 Benign. Variant got -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.050477546 < 0.5 .
• BP6: Variant M-4561-T-C is Benign according to our data. Variant chrM-4561-T-C is described in ClinVar as [Benign]. Clinvar id is 692463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0063
• BS2: High AC in GnomadMitoHomoplasmic at 486

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND2	ENST00000361453.3	c.92T>C	p.Val31Ala	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: 0.0063 AC: 386

Gnomad homoplasmic AF: 0.0086 AC: 486 AN: 56421

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56421

Alfa AF: 0.0288 Hom.: 126

Mitomap

No disease associated.

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.4561T>C (YP_003024027.1:p.Val31Ala) variant in MTND2 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.050
Hmtvar	Benign	0.14
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.54	T
DEOGEN2	Benign	0.051	T
LIST_S2	Benign	0.41	T
MutationAssessor	Benign	0.10	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-2.2	N
Sift4G	Benign	0.22	T
GERP RS		2.5
Varity_R		0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41376350; hg19: chrM-4562;