chrM-10398-A-T

Variant names:

• chrM-10398-A-T
• rs2853826
• ENST00000361227.2:c.340A>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361227.2(MT-ND3):​c.340A>T​(p.Thr114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/8 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. T114A) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 7)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.022
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.338
• Publications: 188 publications found

Genes affected

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.022281682 < 0.5 .
• BP6: Variant M-10398-A-T is Benign according to our data. Variant chrM-10398-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 693288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 13

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361227.2. 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-ND3	ENST00000361227.2	TSL:6	c.340A>T	p.Thr114Ser	missense	Exon 1 of 1	ENSP00000355206.2
	MT-ND4L	ENST00000361335.1	TSL:6	c.-72A>T		upstream_gene	N/A	ENSP00000354728.1
	MT-TR	ENST00000387439.1	TSL:6	n.-7A>T		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00010 AC: 7

Gnomad homoplasmic AF: 0.00023 AC: 13 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.0000798 Hom.: 6986

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.022
Hmtvar	Benign	0.090
AlphaMissense	Benign	0.095
DEOGEN2	Benign	0.18	T
LIST_S2	Benign	0.68	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.34
PROVEAN	Benign	-1.4	N
Sift	Benign	0.070	T
Sift4G	Uncertain	0.054	T
Mutation Taster		=95/5	polymorphism

Other links and lift over

dbSNP: rs2853826; hg19: chrM-10399;