8-144051482-C-CG

Position:

• chr8-144051482-C-CG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000618853.5(OPLAH):​c.3721-11_3721-10insC variant causes a splice polypyrimidine tract, 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 ENST00000618853.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

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]

(HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
OPLAH	NM_017570.5	c.3721-11_3721-10insC		splice_polypyrimidine_tract_variant, intron_variant		ENST00000618853.5	NP_060040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5	c.3721-11_3721-10insC		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017570.5	ENSP00000480476	P1
	ENST00000528912.1	n.1359dup		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 3225 AN: 23052 Hom.: 98 Cov.: 29

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

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

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

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

Submissions by phenotype

5-Oxoprolinase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 27, 2021	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs782568024; hg19: chr8-145106383;