ENST00000361227.2:c.145G>A

Variant names:

• chrM-10203-G-A
• rs1556423781
• ENST00000361227.2:c.145G>A

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.145G>A​(p.Val49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 54)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.017
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.0210
• 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: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.016751064 < 0.5 .
• BP6: Variant M-10203-G-A is Benign according to our data. Variant chrM-10203-G-A is described in ClinVar as [Benign]. Clinvar id is 693272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 31

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND3	unassigned_transcript_4808	c.145G>A	p.Val49Ile	missense_variant	Exon 1 of 1
TRNR	unassigned_transcript_4809	c.-202G>A		upstream_gene_variant
COX3	unassigned_transcript_4806	c.*213G>A		downstream_gene_variant
TRNG	unassigned_transcript_4807	c.*145G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND3	ENST00000361227.2	c.145G>A	p.Val49Ile	missense_variant	Exon 1 of 1	6		ENSP00000355206.2
MT-CO3	ENST00000362079.2	c.*213G>A		downstream_gene_variant		6		ENSP00000354982.2
MT-TR	ENST00000387439.1	n.-202G>A		upstream_gene_variant		6
MT-TG	ENST00000387429.1	n.*145G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00090 AC: 54

Gnomad homoplasmic AF: 0.00055 AC: 31 AN: 56407

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56407

Alfa AF: 0.000779 Hom.: 3

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.10203G>A (YP_003024033.1:p.Val49Ile) variant in MTND3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.017
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.38	T
DEOGEN2	Benign	0.14	T
LIST_S2	Benign	0.52	T
MutationAssessor	Benign	-0.91	N
PhyloP100		-0.021
PROVEAN	Benign	0.94	N
Sift	Benign	0.28	T
Sift4G	Benign	0.065	T
GERP RS		-1.2
Varity_R		0.17
Mutation Taster		=77/23	polymorphism

Other links and lift over

dbSNP: rs1556423781; hg19: chrM-10204; COSMIC: COSV100677639; COSMIC: COSV100677639;