8-144051491-GC-G

Position:

• chr8-144051491-GC-G

Variant summary

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

The ENST00000618853.5(OPLAH):​c.3721-20del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (585 hom., cov: 12)
  • Exomes 𝑓: 0.0026 (200 hom.)
• Consequence: OPLAH ENST00000618853.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.48

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 8-144051491-GC-G is Benign according to our data. Variant chr8-144051491-GC-G is described in ClinVar as [Benign]. Clinvar id is 1169394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5	c.3721-20del		intron_variant		1	NM_017570.5	ENSP00000480476	P1
	ENST00000528912.1	n.1360del		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4357 AN: 139156 Hom.: 585 Cov.: 12

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000430

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.000549

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.00208 AC: 247 AN: 118788 Hom.: 14 AF XY: 0.00168 AC XY: 112 AN XY: 66660

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000150

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.00104

GnomAD4 exome AF: 0.00263 AC: 3271 AN: 1241924 Hom.: 200 Cov.: 10 AF XY: 0.00236 AC XY: 1445 AN XY: 611582

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.00548

Gnomad4 ASJ exome AF: 0.000367

Gnomad4 EAS exome AF: 0.0000553

Gnomad4 SAS exome AF: 0.000786

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.000259

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.0313 AC: 4364 AN: 139218 Hom.: 585 Cov.: 12 AF XY: 0.0309 AC XY: 2107 AN XY: 68264

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000430

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000549

Gnomad4 OTH AF: 0.0257

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	Fulgent Genetics, Fulgent Genetics	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

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: rs148937107; hg19: chr8-145106392; COSMIC: COSV66298033; COSMIC: COSV66298033;