rs2853826

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrM-10398-A-G
• chrM-10398-A-T

Variant summary

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

The ENST00000361227.2(MT-ND3):​c.340A>G​(p.Thr114Ala) 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T114I) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.42 (AC: 25902)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.040
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 Invasive-Breast-Cancer-risk-factor-AD-PD-BD-lithium-response-Type-2-DM,PD-protective-factor-/-longevity-/-altered-cell-pH-/-metabolic-syndrome-/-breast-cancer-risk-/-Leigh-Syndrome-risk-/-ADHD-/-cognitive-decline-/-SCA2-age-of-onset-/-Fuchs-endothelial-corneal-dystrophy
• 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 -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.040168878 < 0.5 .
• BP6: Variant M-10398-A-G is Benign according to our data. Variant chrM-10398-A-G is described in ClinVar as Benign. ClinVar VariationId is 9713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.42369998

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>G	p.Thr114Ala	missense	Exon 1 of 1	ENSP00000355206.2
	MT-ND4L	ENST00000361335.1	TSL:6	c.-72A>G		upstream_gene	N/A	ENSP00000354728.1
	MT-TR	ENST00000387439.1	TSL:6	n.-7A>G		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.42 AC: 25902

Gnomad homoplasmic AF: 0.42 AC: 23506 AN: 56170

Gnomad heteroplasmic AF: 0.00014 AC: 8 AN: 56170

Alfa AF: 0.139 Hom.: 6986

Mitomap

Disease(s): Invasive-Breast-Cancer-risk-factor-AD-PD-BD-lithium-response-Type-2-DM,PD-protective-factor-/-longevity-/-altered-cell-pH-/-metabolic-syndrome-/-breast-cancer-risk-/-Leigh-Syndrome-risk-/-ADHD-/-cognitive-decline-/-SCA2-age-of-onset-/-Fuchs-endothelial-corneal-dystrophy

Status: Reported|-lineage-N-marker-except-hg-IJK,Reported|-lineage-L-&-M-marker+-also-hg-IJK

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	-	Parkinson disease, resistance to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.040
Hmtvar	Benign	0.040
AlphaMissense	Benign	0.064
DEOGEN2	Benign	0.18	T
LIST_S2	Uncertain	0.96	D
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.34
PROVEAN	Benign	-1.4	N
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs2853826; hg19: chrM-10399;