chr8-144051482-C-CG

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]
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]

Genome browser will be placed here

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
OPLAHNM_017570.5 linkc.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
OPLAHENST00000618853.5 linkc.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.:
98
Cov.:
29
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.:
2
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.:
88
Cov.:
27
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.:
99
Cov.:
29
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.

Other links and lift over

dbSNP: rs782568024; hg19: chr8-145106383; API