Genetic Variant OPLAH:c.3721-11dupC (chr8-144051482-C-CG) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017570.5(OPLAH):c.3721-11dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 265,872 control chromosomes in the GnomAD database, including 187 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 99 hom., cov: 29)

Exomes 𝑓: 0.088 ( 88 hom. )

Consequence

OPLAH
NM_017570.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.23

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 links:

SMPD5 (HGNC:52275): (sphingomyelin phosphodiesterase 5 (pseudogene)) Predicted to enable sphingomyelin phosphodiesterase activity. Predicted to be involved in ceramide biosynthetic process and sphingomyelin catabolic process. Predicted to act upstream of or within ceramide metabolic process. Predicted to be located in endoplasmic reticulum membrane and mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMPD5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-144051482-C-CG is Benign according to our data. Variant chr8-144051482-C-CG is described in ClinVar as [Benign]. Clinvar id is 1599755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPLAH	NM_017570.5 link	c.3721-11dupC		intron_variant	Intron 26 of 26	ENST00000618853.5	NP_060040.1	O14841

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5 link	c.3721-11dupC		intron_variant	Intron 26 of 26	1	NM_017570.5	ENSP00000480476.1		O14841

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

3225

AN:

23052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.0190

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.0430

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0645

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.167

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0407

AC:

1304

AN:

32016

Hom.:

AF XY:

0.0389

AC XY:

716

AN XY:

18390

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.0692

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0215

Gnomad SAS exome

AF:

0.0300

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0884

AC:

21462

AN:

242806

Hom.:

Cov.:

AF XY:

0.0859

AC XY:

10704

AN XY:

124560

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0655

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.0205

Gnomad4 SAS exome

AF:

0.0592

Gnomad4 FIN exome

AF:

0.0991

Gnomad4 NFE exome

AF:

0.0959

Gnomad4 OTH exome

AF:

0.0884

GnomAD4 genome

AF:

0.140

AC:

3230

AN:

23066

Hom.:

Cov.:

AF XY:

0.134

AC XY:

1515

AN XY:

11300

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.0430

Gnomad4 EAS

AF:

0.0133

Gnomad4 SAS

AF:

0.0617

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

5-Oxoprolinase deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 27, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over