8-144051482-CGGGGGG-CG

Variant names:

• chr8-144051482-CGGGGG-C
• rs782568024
• NM_017570.5:c.3721-15_3721-11delCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017570.5(OPLAH):​c.3721-15_3721-11delCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 256,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: OPLAH NM_017570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• 5-oxoprolinase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000293498 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017570.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPLAH	NM_017570.5	MANE Select	c.3721-15_3721-11delCCCCC		intron	N/A	NP_060040.1	O14841

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPLAH	ENST00000618853.5	TSL:1 MANE Select	c.3721-15_3721-11delCCCCC		intron	N/A	ENSP00000480476.1	O14841
	OPLAH	ENST00000894965.1		c.3751-15_3751-11delCCCCC		intron	N/A	ENSP00000565024.1
	OPLAH	ENST00000919620.1		c.3745-15_3745-11delCCCCC		intron	N/A	ENSP00000589679.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000234 AC: 6 AN: 256838 Hom.: 0 AF XY: 0.00000759 AC XY: 1 AN XY: 131774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5552

American (AMR) AF: 0.00 AC: 0 AN: 8834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4862

East Asian (EAS) AF: 0.00 AC: 0 AN: 10204

South Asian (SAS) AF: 0.00 AC: 0 AN: 18440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 814

European-Non Finnish (NFE) AF: 0.0000323 AC: 6 AN: 185810

Other (OTH) AF: 0.00 AC: 0 AN: 11802

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782568024; hg19: chr8-145106383;