rs28358280

Variant names:

• chrM-10550-A-G
• rs28358280
• unassigned_transcript_4810:c.81A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.037 (AC: 2254)
• Consequence: ND4L missense
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -0.873

Genes affected

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]

ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

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]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: High frequency in mitomap database: 0.0369

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4L	unassigned_transcript_4810	c.81A>G	p.Ile27Met	missense_variant	Exon 1 of 1
ND4	unassigned_transcript_4811	c.-210A>G		upstream_gene_variant
ND3	unassigned_transcript_4808	c.*146A>G		downstream_gene_variant
TRNR	unassigned_transcript_4809	c.*81A>G		downstream_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: 0.037 AC: 2254

Gnomad homoplasmic AF: 0.049 AC: 2739 AN: 56418

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56418

Alfa AF: 0.0936 Hom.: 4264

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
GERP RS		3.7
Varity_R		0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28358280; hg19: chrM-10551;