7-43639603-AC-GT

Variant names:

• chr7-43639603-AC-GT
• NM_018224.4:c.419_420delGTinsAC
• COA1 p.Gly140Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018224.4(COA1):​c.419_420delGTinsAC​(p.Gly140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COA1 NM_018224.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 0 publications found

Genes affected

COA1 (HGNC:21868): (cytochrome c oxidase assembly factor 1) Involved in mitochondrial cytochrome c oxidase assembly and mitochondrial respiratory chain complex I assembly. Located in cytosol and mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

STK17A (HGNC:11395): (serine/threonine kinase 17a) This gene is a member of the DAP kinase-related apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. The protein has apoptosis-inducing activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018224.4. 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
	COA1	NM_018224.4	MANE Select	c.419_420delGTinsAC	p.Gly140Asp	missense	N/A	NP_060694.2	Q9GZY4
	COA1	NM_001321197.2		c.419_420delGTinsAC	p.Gly140Asp	missense	N/A	NP_001308126.1	Q9GZY4
	COA1	NM_001321198.2		c.419_420delGTinsAC	p.Gly140Asp	missense	N/A	NP_001308127.1	Q9GZY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA1	ENST00000223336.11	TSL:2 MANE Select	c.419_420delGTinsAC	p.Gly140Asp	missense	N/A	ENSP00000223336.6	Q9GZY4
	COA1	ENST00000395879.5	TSL:1	c.419_420delGTinsAC	p.Gly140Asp	missense	N/A	ENSP00000379218.1	Q9GZY4
	COA1	ENST00000896980.1		c.437_438delGTinsAC	p.Gly146Asp	missense	N/A	ENSP00000567039.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.98

Splicing

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

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

Other links and lift over

hg19: chr7-43679202;