rs1556424118

Variant names:

• chrM-12493-A-G
• rs1556424118
• unassigned_transcript_4815:c.157A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.027
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.97

Genes affected

ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BS2: High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND5	unassigned_transcript_4815	c.157A>G	p.Ile53Val	missense_variant	Exon 1 of 1
TRNL2	unassigned_transcript_4814	c.*157A>G		downstream_gene_variant
TRNS2	unassigned_transcript_4813	c.*228A>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: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 11, 2017

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.027
Hmtvar	Benign	0.21
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.58	T
GERP RS		-6.5
Varity_R		0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556424118; hg19: chrM-12494;