rs185836803

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017570.5(OPLAH):c.3265G>A(p.Val1089Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 1,562,106 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 78 hom. )

Consequence

OPLAH
NM_017570.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 2.74

Publications

10 publications found

Variant links:

Genes affected

OPLAH (HGNC:8149): (5-oxoprolinase, ATP-hydrolysing) The protein encoded by this gene acts as a homodimer, using ATP hydrolysis to catalyze the conversion of 5-oxo-L-proline to L-glutamate. Defects in this gene are a cause of 5-oxoprolinase deficiency (OPLAHD). [provided by RefSeq, Jun 2012]

OPLAH Gene-Disease associations (from GenCC):

5-oxoprolinase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

OPLAH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009413838).

BP6

Variant 8-144052487-C-T is Benign according to our data. Variant chr8-144052487-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 39636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00839 (1277/152184) while in subpopulation AMR AF = 0.0154 (235/15300). AF 95% confidence interval is 0.0137. There are 7 homozygotes in GnomAd4. There are 623 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017570.5. 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
	OPLAH	NM_017570.5	MANE Select	c.3265G>A	p.Val1089Ile	missense	Exon 23 of 27	NP_060040.1	O14841

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPLAH	ENST00000618853.5	TSL:1 MANE Select	c.3265G>A	p.Val1089Ile	missense	Exon 23 of 27	ENSP00000480476.1	O14841
OPLAH	ENST00000894965.1		c.3265G>A	p.Val1089Ile	missense	Exon 23 of 27	ENSP00000565024.1
OPLAH	ENST00000919620.1		c.3289G>A	p.Val1097Ile	missense	Exon 23 of 27	ENSP00000589679.1

Frequencies

GnomAD3 genomes

AF:

0.00839

AC:

1276

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00768

GnomAD2 exomes

AF:

0.00948

AC:

1559

AN:

164386

AF XY:

0.00859

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00712

GnomAD4 exome

AF:

0.00968

AC:

13649

AN:

1409922

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

6600

AN XY:

698508

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

32652

American (AMR)

AF:

0.0212

AC:

813

AN:

38424

Ashkenazi Jewish (ASJ)

AF:

0.0000393

AC:

AN:

25442

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37406

South Asian (SAS)

AF:

0.00245

AC:

199

AN:

81190

European-Finnish (FIN)

AF:

0.0124

AC:

468

AN:

37754

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0107

AC:

11680

AN:

1092486

Other (OTH)

AF:

0.00734

AC:

432

AN:

58868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

760

1519

2279

3038

3798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00839

AC:

1277

AN:

152184

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

623

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41534

American (AMR)

AF:

0.0154

AC:

235

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

782

AN:

67984

Other (OTH)

AF:

0.00760

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00700

Hom.:

Bravo

AF:

0.00847

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00168

AC:

ESP6500EA

AF:

0.00787

AC:

ExAC

AF:

0.00635

AC:

728

Asia WGS

AF:

0.00116

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

5-Oxoprolinase deficiency (5)

not provided (1)

OPLAH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0094

MetaSVM

Uncertain

-0.14

PhyloP100

2.7

PrimateAI

Pathogenic

0.86

Sift4G

Uncertain

0.048

Polyphen

0.99

Vest4

0.31

MVP

0.35

ClinPred

0.031

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.59

gMVP

0.71

Mutation Taster

=91/9

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over