14-22771504-T-TAGCAGCAGC

Variant names:

• chr14-22771504-T-TAGCAGCAGC
• rs148216086
• NM_005015.5:c.1259_1267dupGCAGCAGCA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_005015.5(OXA1L):​c.1259_1267dupGCAGCAGCA​(p.Ser420_Ser422dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,690 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OXA1L NM_005015.5 disruptive_inframe_insertion
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_005015.5.

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.1259_1267dupGCAGCAGCA	p.Ser420_Ser422dup	disruptive_inframe_insertion	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.1259_1267dupGCAGCAGCA	p.Ser420_Ser422dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000483491.2	Q15070-1
	OXA1L	ENST00000285848.9	TSL:1	c.1439_1447dupGCAGCAGCA	p.Ser480_Ser482dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000285848.5	J3KNA0
	OXA1L	ENST00000937832.1		c.1253_1261dupGCAGCAGCA	p.Ser418_Ser420dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000607891.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459690 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726198

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110072

Other (OTH) AF: 0.00 AC: 0 AN: 60324

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

Other links and lift over

dbSNP: rs148216086; hg19: chr14-23240713;