14-22771504-T-TAGC

Variant names:

• chr14-22771504-T-TAGC
• rs148216086
• NM_005015.5:c.1265_1267dupGCA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_005015.5(OXA1L):​c.1265_1267dupGCA​(p.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 0.272 in 1,611,336 control chromosomes in the GnomAD database, including 60,630 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4869 hom., cov: 24)
  • Exomes 𝑓: 0.27 (55761 hom.)
• Consequence: OXA1L NM_005015.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11
• Publications: 9 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: Benign. The variant received -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005015.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 14-22771504-T-TAGC is Benign according to our data. Variant chr14-22771504-T-TAGC is described in ClinVar as Benign. ClinVar VariationId is 403461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXA1L	NM_005015.5	MANE Select	c.1265_1267dupGCA	p.Ser422dup	disruptive_inframe_insertion	Exon 10 of 10	NP_005006.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXA1L	ENST00000612549.6	TSL:1 MANE Select	c.1265_1267dupGCA	p.Ser422dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000483491.2
	OXA1L	ENST00000285848.9	TSL:1	c.1445_1447dupGCA	p.Ser482dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000285848.5
	OXA1L	ENST00000358043.5	TSL:2	c.1217_1219dupGCA	p.Ser406dup	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000350740.5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37865 AN: 151794 Hom.: 4865 Cov.: 24

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.257 AC: 64521 AN: 251312 AF XY: 0.266

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.274 AC: 400026 AN: 1459424 Hom.: 55761 Cov.: 33 AF XY: 0.278 AC XY: 201730 AN XY: 726078

African (AFR) AF: 0.205 AC: 6854 AN: 33450

American (AMR) AF: 0.224 AC: 10039 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6332 AN: 26118

East Asian (EAS) AF: 0.152 AC: 6027 AN: 39686

South Asian (SAS) AF: 0.361 AC: 31122 AN: 86144

European-Finnish (FIN) AF: 0.229 AC: 12224 AN: 53384

Middle Eastern (MID) AF: 0.287 AC: 1654 AN: 5762

European-Non Finnish (NFE) AF: 0.279 AC: 309628 AN: 1109850

Other (OTH) AF: 0.268 AC: 16146 AN: 60312

GnomAD4 genome AF: 0.249 AC: 37896 AN: 151912 Hom.: 4869 Cov.: 24 AF XY: 0.249 AC XY: 18478 AN XY: 74266

African (AFR) AF: 0.206 AC: 8552 AN: 41440

American (AMR) AF: 0.233 AC: 3559 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3466

East Asian (EAS) AF: 0.147 AC: 759 AN: 5156

South Asian (SAS) AF: 0.364 AC: 1757 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2206 AN: 10562

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19170 AN: 67900

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.192 Hom.: 604

Asia WGS AF: 0.277 AC: 964 AN: 3478

EpiCase AF: 0.290

EpiControl AF: 0.285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=79/21	polymorphism (auto)

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; COSMIC: COSV53536274; COSMIC: COSV53536274;