rs193302927

Variant names:

• chrM-10238-T-C
• rs193302927
• ENST00000361227.2:c.180T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The ENST00000361227.2(MT-ND3):​c.180T>C​(p.Ile60Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.057 (AC: 3480)
• Consequence: MT-ND3 ENST00000361227.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.56
• Publications: 10 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]

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: Benign. The variant received -11 ACMG points.

• BP6: Variant M-10238-T-C is Benign according to our data. Variant chrM-10238-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3911675.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.56 with no splicing effect.
• BA1: High frequency in mitomap database: 0.056900002

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND3	unassigned_transcript_4808	c.180T>C	p.Ile60Ile	synonymous_variant	Exon 1 of 1
ND4L	unassigned_transcript_4810	c.-232T>C		upstream_gene_variant
TRNR	unassigned_transcript_4809	c.-167T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND3	ENST00000361227.2	c.180T>C	p.Ile60Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000355206.2
MT-ND4L	ENST00000361335.1	c.-232T>C		upstream_gene_variant		6		ENSP00000354728.1
MT-CO3	ENST00000362079.2	c.*248T>C		downstream_gene_variant		6		ENSP00000354982.2

Frequencies

Mitomap GenBank AF: 0.057 AC: 3480

Gnomad homoplasmic AF: 0.025 AC: 1401 AN: 56425

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56425

Alfa AF: 0.0354 Hom.: 1691

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.6
Mutation Taster		=80/20	polymorphism

Other links and lift over

dbSNP: rs193302927; hg19: chrM-10239;