rs1556423587

Variant names:

• chrM-9006-A-G
• rs1556423587
• ENST00000361899.2:c.480A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361899.2(MT-ATP6):​c.480A>G​(p.Leu160Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0013 (AC: 80)
• Consequence: MT-ATP6 ENST00000361899.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -5.76
• Publications: 0 publications found

Genes affected

MT-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]

MT-CO3 (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]

MT-CO3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP6: Variant M-9006-A-G is Benign according to our data. Variant chrM-9006-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 446022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.76 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 143

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6	unassigned_transcript_4805	c.480A>G	p.Leu160Leu	synonymous_variant	Exon 1 of 1
COX3	unassigned_transcript_4806	c.-201A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ATP6	ENST00000361899.2	c.480A>G	p.Leu160Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354632.2
MT-CO3	ENST00000362079.2	c.-201A>G		upstream_gene_variant		6		ENSP00000354982.2

Frequencies

Mitomap GenBank AF: 0.0013 AC: 80

Gnomad homoplasmic AF: 0.0025 AC: 143 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00290 Hom.: 13

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 09, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.8
Mutation Taster		=45/55	disease causing

Other links and lift over

dbSNP: rs1556423587; hg19: chrM-9007;