M-9355-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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: 0)
• Consequence: COX3 missense
• Scores: Apogee2 Benign 0.037
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.149A>T	p.Asn50Ile	missense_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.*148A>T		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: 0

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar ataxia;C0311394:Difficulty walking;C0349588:Short stature;C1384666:Hearing impairment;C2242577:Oromandibular dystonia Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sleep apnea;C0162557:Acute liver failure;C0392525:Nephrolithiasis;C0424551:Exercise intolerance;C0518656:Chronic fatigue;C1403035:Subcutaneous lipoma;C4021546:Abnormal mitochondria in muscle tissue;C4024664:Moderate sensorineural hearing impairment Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

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	0.037
Hmtvar	Benign	0.31
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.41	T
DEOGEN2	Benign	0.0036	T
LIST_S2	Benign	0.65	T
MutationAssessor	Benign	-1.2	N
PROVEAN	Benign	2.1	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.58	T
GERP RS		2.0
Varity_R		0.39

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;