Variant 8-144051492-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017570.5(OPLAH):c.3721-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 206 hom., cov: 12)

Exomes 𝑓: 0.037 ( 130 hom. )

Failed GnomAD Quality Control

Consequence

OPLAH
NM_017570.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.48

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 8-144051492-C-G is Benign according to our data. Variant chr8-144051492-C-G is described in ClinVar as [Benign]. Clinvar id is 1600681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPLAH	NM_017570.5 link	c.3721-20G>C		intron_variant		ENST00000618853.5	NP_060040.1	O14841

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5 link	c.3721-20G>C		intron_variant		1	NM_017570.5	ENSP00000480476.1		O14841

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

5310

AN:

66304

Hom.:

202

Cov.:

FAILED QC

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0228

Gnomad AMR

AF:

0.0505

Gnomad ASJ

AF:

0.0258

Gnomad EAS

AF:

0.0103

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.0294

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0793

GnomAD3 exomes

AF:

0.0609

AC:

4168

AN:

68406

Hom.:

295

AF XY:

0.0540

AC XY:

2096

AN XY:

38836

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.0679

Gnomad EAS exome

AF:

0.0137

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0440

Gnomad OTH exome

AF:

0.0535

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0370

AC:

12578

AN:

339626

Hom.:

130

Cov.:

AF XY:

0.0385

AC XY:

6584

AN XY:

171086

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.0504

Gnomad4 ASJ exome

AF:

0.0459

Gnomad4 EAS exome

AF:

0.0122

Gnomad4 SAS exome

AF:

0.0879

Gnomad4 FIN exome

AF:

0.0449

Gnomad4 NFE exome

AF:

0.0253

Gnomad4 OTH exome

AF:

0.0476

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0803

AC:

5324

AN:

66328

Hom.:

206

Cov.:

AF XY:

0.0782

AC XY:

2484

AN XY:

31754

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.0505

Gnomad4 ASJ

AF:

0.0258

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.0250

Gnomad4 FIN

AF:

0.0279

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.00365

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

5-Oxoprolinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.90

DANN

Benign

0.41

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