chr14-22771503-CT-CTAGCAGCAG

Variant names:

• chr14-22771504-T-TAGCAGCAG
• NM_005015.5:c.1255_1262dupAGCAGCAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005015.5(OXA1L):​c.1255_1262dupAGCAGCAG​(p.Ser421ArgfsTer50) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: OXA1L NM_005015.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

OXA1L (HGNC:8526): (OXA1L mitochondrial inner membrane protein) This gene encodes an evolutionarily conserved protein that is localized to the inner mitochondrial membrane. The encoded protein is essential for the translocation of the N-terminal tail of subunit 2 of cytochrome c oxidase, and is involved in the assembly of the cytochrome c oxidase and ATPase complexes of the mitochondrial respiratory chain. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005015.5. 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
	OXA1L	NM_005015.5	MANE Select	c.1255_1262dupAGCAGCAG	p.Ser421ArgfsTer50	frameshift	Exon 10 of 10	NP_005006.4	Q15070-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXA1L	ENST00000612549.6	TSL:1 MANE Select	c.1255_1262dupAGCAGCAG	p.Ser421ArgfsTer50	frameshift	Exon 10 of 10	ENSP00000483491.2	Q15070-1
	OXA1L	ENST00000285848.9	TSL:1	c.1435_1442dupAGCAGCAG	p.Ser481ArgfsTer50	frameshift	Exon 10 of 10	ENSP00000285848.5	J3KNA0
	OXA1L	ENST00000937832.1		c.1249_1256dupAGCAGCAG	p.Ser419ArgfsTer50	frameshift	Exon 10 of 10	ENSP00000607891.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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: chr14-23240713;