dbSNP rs148216086: OXA1L:p.Ser422dup (chr14-22771504-T-TAGC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Publications

9 publications found

Variant links:

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]

OXA1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXA1L	NM_005015.5 link	c.1265_1267dupGCA	p.Ser422dup	disruptive_inframe_insertion	Exon 10 of 10	ENST00000612549.6	NP_005006.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXA1L	ENST00000612549.6 link	c.1265_1267dupGCA	p.Ser422dup	disruptive_inframe_insertion	Exon 10 of 10	1	NM_005015.5	ENSP00000483491.2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37865

AN:

151794

Hom.:

4865

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.278

AC XY:

201730

AN XY:

726078

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13872

27744

41615

55487

69359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10300

20600

30900

41200

51500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.249

AC:

37896

AN:

151912

Hom.:

4869

Cov.:

AF XY:

0.249

AC XY:

18478

AN XY:

74266

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19170

AN:

67900

Other (OTH)

AF:

0.278

AC:

587

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1433

2866

4299

5732

7165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over