Variant chr8-144051480-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017570.5(OPLAH):c.3721-8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OPLAH
NM_017570.5 splice_region, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-144051480-C-G is Benign according to our data. Variant chr8-144051480-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658965.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPLAH	NM_017570.5 link	c.3721-8G>C		splice_region_variant, 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.3721-8G>C		splice_region_variant, intron_variant		1	NM_017570.5	ENSP00000480476.1		O14841

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

76930

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000903

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000185

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

79396

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

45500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000832

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00166

AC:

530

AN:

318324

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

320

AN XY:

159810

show subpopulations

Gnomad4 AFR exome

AF:

0.000172

Gnomad4 AMR exome

AF:

0.00209

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.000436

Gnomad4 SAS exome

AF:

0.00855

Gnomad4 FIN exome

AF:

0.00235

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000751

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000286

AC:

AN:

76934

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

AN XY:

35692

show subpopulations

Gnomad4 AFR

AF:

0.000903

Gnomad4 AMR

AF:

0.000477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.000185

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

OPLAH: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.0

DANN

Benign

0.65

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