chrM-10159-C-A

Variant names:

• chrM-10159-C-A
• rs1603222701
• ENST00000361227.2:c.101C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The ENST00000361227.2(MT-ND3):​c.101C>A​(p.Ser34Tyr) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S34P) has been classified as Pathogenic.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.14
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.639
• 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 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PM5: Other missense variant is known to change same aminoacid residue: Variant chrM-10158-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 9714.Status of the report is reviewed_by_expert_panel, 3 stars.
• BP4: Apogee2 supports a benign effect, 0.1375038 < 0.5 .

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.101C>A	p.Ser34Tyr	missense	Exon 1 of 1	ENSP00000355206.2	P03897
	MT-CO3	ENST00000362079.2	TSL:6	c.*169C>A		downstream_gene	N/A	ENSP00000354982.2	P00414
	MT-TR	ENST00000387439.1	TSL:6	n.-246C>A		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.14
Hmtvar	Pathogenic	0.48
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.39	T
DEOGEN2	Benign	0.23	T
LIST_S2	Benign	0.52	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.64
PROVEAN	Benign	-1.4	N
Sift	Benign	0.56	T
Sift4G	Benign	0.14	T
GERP RS		0.81
Varity_R		0.14

Other links and lift over

dbSNP: rs1603222701; hg19: chrM-10160;