rs193302928

Variant names:

• chrM-10321-T-C
• rs193302928
• unassigned_transcript_4808:c.263T>C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0085 (AC: 522)
• Consequence: ND3 missense
• Scores: Apogee2 Benign 0.038
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 No linked disesase in Mitomap
• Conservation: PhyloP100: 2.69

Genes affected

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]

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)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant M-10321-T-C is Benign according to our data. Variant chrM-10321-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0085
• BS2: High AC in GnomadMitoHomoplasmic at 1070

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND3	unassigned_transcript_4808	c.263T>C	p.Val88Ala	missense_variant	Exon 1 of 1
ND4L	unassigned_transcript_4810	c.-149T>C		upstream_gene_variant
TRNR	unassigned_transcript_4809	c.-84T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0085 AC: 522

Gnomad homoplasmic AF: 0.019 AC: 1070 AN: 56424

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56424

Alfa AF: 0.00235 Hom.: 92

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 12, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.10321T>C (YP_003024033.1:p.Val88Ala) 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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.038
Hmtvar	Benign	0.090
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
DEOGEN2	Benign	0.35	T
LIST_S2	Benign	0.40	T
MutationAssessor	Benign	0.38	N
PROVEAN	Benign	-2.0	N
Sift	Uncertain	0.027	D
Sift4G	Benign	0.14	T
GERP RS		3.1
Varity_R		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193302928; hg19: chrM-10322;