Genetic Variant MT-ND5:p.Asp393His (chrM-13513-GAC-CAT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The unassigned_transcript_4815(ND5):c.1177_1179delGACinsCAT (p.Asp393His) variant causes a missense change. Note: unassigned_transcript_4815 is not a MANE Select or MANE Plus Clinical transcript for ND5; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. No reliable population frequency data is available for this variant in the Mitomap database. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 9.29). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. A different missense at the same amino acid position has been reported as Pathogenic/Likely Pathogenic in ClinVar: p.D393N: Pathogenic (ClinVar VariationId 9702, 3 stars)

Frequency

Mitomap GenBank:

Absent

Consequence

ND5
unassigned_transcript_4815 missense

Scores

Clinical Significance

Not reported in ClinVar

No linked disesase in Mitomap

Conservation

PhyloP100: 9.29

Publications

0 publications found

Variant links:

Genes affected

MT-ND5 (HGNC:7461): (NADH dehydrogenase subunit 5) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Jul 2025]

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

MT-ND5 links:

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new If you want to explore the variant's impact on the transcript unassigned_transcript_4815, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Mitochondrial variant absent from Mitomap — O3 moderate; Mitochondrial variant — absent from Mitomap (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000361567.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MT-ND5 ENST00000361567.2	TSL:6	c.1177_1179delGACinsCAT p.Asp393His	missense	N/A	Prot: ENSP00000354813.2 UniProt: P03915

MT-ND5 ENST00000361567.2

TSL:6

HGVSc / HGVSpc.1177_1179delGACinsCATp.Asp393His

Exon rankN/A

missense

Prot: ENSP00000354813.2UniProt: P03915

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage

Showing 0 sources

Tested, but no data found:Mitomap GenBank

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	9.3

Showing 1 of 1 scores

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Mitomap

ClinVar

Computational Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence