rs193302928

chrM-10321-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The ENST00000361227.2(MT-ND3):c.263T>C(p.Val88Ala) 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 Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0085 (AC: 522)
• Consequence: MT-ND3 ENST00000361227.2 missense
• Scores: Apogee2 Benign 0.038
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 2.69

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.038404237 < 0.5 .
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND3	ENST00000361227.2	c.263T>C	p.Val88Ala	missense_variant	1/1			P1

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

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 -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Aug 12, 2015

- -

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
MutationTaster	Benign	1.0	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;