ENST00000361567.2:c.1444A>G

Variant names:

• chrM-13780-A-G
• rs41358152
• ENST00000361567.2:c.1444A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The ENST00000361567.2(MT-ND5):​c.1444A>G​(p.Ile482Val) variant causes a missense change involving the alteration of a 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I482T) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.019 (AC: 1142)
• Consequence: MT-ND5 ENST00000361567.2 missense
• Scores: Apogee2 Benign 0.0033
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 8.67
• Publications: 10 publications found

Genes affected

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND5 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.003263095 < 0.5 .
• BP6: Variant M-13780-A-G is Benign according to our data. Variant chrM-13780-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 693608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.0187

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.1444A>G	p.Ile482Val	missense_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND5	ENST00000361567.2	c.1444A>G	p.Ile482Val	missense_variant	Exon 1 of 1	6		ENSP00000354813.2

Frequencies

Mitomap GenBank AF: 0.019 AC: 1142

Gnomad homoplasmic AF: 0.018 AC: 1043 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.0142 Hom.: 185

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Leigh syndrome Benign:1

Oct 17, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.13780A>G (YP_003024036.1:p.Ile482Val) variant in MTND5 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	0.0033
Hmtvar	Benign	0.17
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
DEOGEN2	Benign	0.0057	T
LIST_S2	Benign	0.54	T
MutationAssessor	Benign	0.76	N
PhyloP100		8.7
PROVEAN	Benign	-0.030	N
Sift4G	Uncertain	0.0040	D
GERP RS		4.5
Varity_R		0.40
Mutation Taster		=70/30	polymorphism

Other links and lift over

dbSNP: rs41358152; hg19: chrM-13781;