chrM-13637-A-G

Variant names:

• chrM-13637-A-G
• rs200855215
• ENST00000361567.2:c.1301A>G
• MT-ND5 p.Gln434Arg

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The ENST00000361567.2(MT-ND5):​c.1301A>G​(p.Gln434Arg) variant causes a missense change involving the alteration of a non-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 Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0097 (AC: 595)
• Consequence: MT-ND5 ENST00000361567.2 missense
• Scores: Apogee2 Benign 0.055
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 Possible-LHON-factor
• Conservation: PhyloP100: 0.242
• Publications: 17 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: G2P, Orphanet
• 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 -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.05537165 < 0.5 .
• BP6: Variant M-13637-A-G is Benign according to our data. Variant chrM-13637-A-G is described in ClinVar as Benign. ClinVar VariationId is 65511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: High frequency in mitomap database: 0.0097
• BS2: High AC in GnomadMitoHomoplasmic at 643

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
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.1301A>G	p.Gln434Arg	missense	Exon 1 of 1	ENSP00000354813.2	P03915

Frequencies

Mitomap GenBank AF: 0.0097 AC: 595

Gnomad homoplasmic AF: 0.011 AC: 643 AN: 56431

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56431

Alfa AF: 0.00574 Hom.: 63

Mitomap

Disease(s): Possible-LHON-factor

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	-	Leber optic atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.055
Hmtvar	Benign	0.19
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.51	T
DEOGEN2	Benign	0.065	T
LIST_S2	Benign	0.26	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.24
PROVEAN	Uncertain	-2.4	N
Sift4G	Benign	0.077	T
Varity_R		0.64
Mutation Taster		=100/0	polymorphism

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200855215;

hg19: chrM-13638;