rs1603222711

Variant names:

• chrM-10176-G-A
• rs1603222711
• ENST00000361227.2:c.118G>A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The ENST00000361227.2(MT-ND3):​c.118G>A​(p.Gly40Ser) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Pathogenic 0.83
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.68
• Publications: 0 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-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

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

TRNG (HGNC:7486): (mitochondrially encoded tRNA glycine)

TRNG Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Apogee2 supports a deletorius effect, 0.826584 >= 0.5 .
• PP5: Variant M-10176-G-A is Pathogenic according to our data. Variant chrM-10176-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3781322.Status of the report is criteria_provided_single_submitter, 1 stars.

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.118G>A	p.Gly40Ser	missense	Exon 1 of 1	ENSP00000355206.2	P03897
	MT-CO3	ENST00000362079.2	TSL:6	c.*186G>A		downstream_gene	N/A	ENSP00000354982.2	P00414
	MT-TR	ENST00000387439.1	TSL:6	n.-229G>A		upstream_gene	N/A

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56431

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56431

Alfa AF: 0.000111 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.83
Hmtvar	Pathogenic	0.88
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.0051	T
DEOGEN2	Pathogenic	0.84	D
LIST_S2	Uncertain	0.94	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		4.7
PROVEAN	Pathogenic	-6.0	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
GERP RS		5.1
Varity_R		0.64
Mutation Taster		=35/65	disease causing

Other links and lift over

dbSNP: rs1603222711; hg19: chrM-10177; COSMIC: COSV107450084; COSMIC: COSV107450084;