rs1556423663

Variant names:

• chrM-9355-A-G
• rs1556423663
• unassigned_transcript_4806:c.149A>G

Your query was ambiguous. Multiple possible variants found:

• chrM-9355-A-G
• chrM-9355-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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

• Frequency: Mitomap GenBank: 𝑓 0.00040 (AC: 23)
• Consequence: COX3 missense
• Scores: Apogee2 Benign 0.044
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.212

Genes affected

COX3 (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]

ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-9355-A-G is Benign according to our data. Variant chrM-9355-A-G is described in ClinVar as [Benign]. Clinvar id is 693155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 13

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.149A>G	p.Asn50Ser	missense_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.*148A>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: 0.00040 AC: 23

Gnomad homoplasmic AF: 0.00023 AC: 13 AN: 56429

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56429

Alfa AF: 0.000334 Hom.: 1

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.9355A>G (YP_003024032.1:p.Asn50Ser) variant in MTCO3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.044
Hmtvar	Benign	0.10
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.46	T
DEOGEN2	Benign	0.0055	T
LIST_S2	Benign	0.71	T
MutationAssessor	Benign	0.24	N
PROVEAN	Benign	0.49	N
Sift	Uncertain	0.028	D
Sift4G	Benign	0.073	T
GERP RS		2.0
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: rs1556423663; hg19: chrM-9356;