rs1556423250

Variant names:

• chrM-7220-T-C
• rs1556423250
• ENST00000361624.2:c.1317T>C
• MT-CO1 p.Arg439Arg

Variant summary

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

The ENST00000361624.2(MT-CO1):​c.1317T>C​(p.Arg439Arg) 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 0.00060 (AC: 37)
• Consequence: MT-CO1 ENST00000361624.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -4.85
• Publications: 0 publications found

Genes affected

MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP6: Variant M-7220-T-C is Benign according to our data. Variant chrM-7220-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 445535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.85 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 22

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361624.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO1	ENST00000361624.2	TSL:6	c.1317T>C	p.Arg439Arg	synonymous	Exon 1 of 1	ENSP00000354499.2	P00395
	MT-TS1	ENST00000387416.2	TSL:6	n.*226A>G		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00060 AC: 37

Gnomad homoplasmic AF: 0.00039 AC: 22 AN: 56364

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56364

Alfa AF: 0.00257 Hom.: 11

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.9
Mutation Taster		=32/68	disease causing

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1556423250;

hg19: chrM-7221;

COSMIC: COSV62294342;

COSMIC: COSV62294342;