8-144051490-GGC-G

Position:

• chr8-144051490-GGC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017570.5(OPLAH):​c.3721-20_3721-19del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,425,738 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (7 hom., cov: 12)
  • Exomes 𝑓: 0.0013 (38 hom.)
• Consequence: OPLAH NM_017570.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.418

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 -10 ACMG points.

• BP6: Variant 8-144051490-GGC-G is Benign according to our data. Variant chr8-144051490-GGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1594896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPLAH	NM_017570.5	c.3721-20_3721-19del		intron_variant		ENST00000618853.5	NP_060040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5	c.3721-20_3721-19del		intron_variant		1	NM_017570.5	ENSP00000480476	P1
	ENST00000528912.1	n.1360_1361del		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 119 AN: 149460 Hom.: 7 Cov.: 12

Gnomad AFR AF: 0.00257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000665 AC: 87 AN: 130828 Hom.: 10 AF XY: 0.000587 AC XY: 43 AN XY: 73236

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.000701

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000783

Gnomad SAS exome AF: 0.000137

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000464

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00130 AC: 1658 AN: 1276182 Hom.: 38 AF XY: 0.00127 AC XY: 795 AN XY: 628042

Gnomad4 AFR exome AF: 0.0604

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.000359

Gnomad4 EAS exome AF: 0.000300

Gnomad4 SAS exome AF: 0.000798

Gnomad4 FIN exome AF: 0.000324

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.000802 AC: 120 AN: 149556 Hom.: 7 Cov.: 12 AF XY: 0.000862 AC XY: 63 AN XY: 73118

Gnomad4 AFR AF: 0.00259

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00101 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

5-Oxoprolinase deficiency Benign:1

Likely 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: rs781891990; hg19: chr8-145106391;