8-144051482-CGGGGGG-CGGGGGGGGGGGGGGTGGGGGGGGGGGG

Variant names:

• chr8-144051482-C-CGGGGGGGGGGGGGGTGGGGGG
• rs782568024
• NM_017570.5:c.3721-11_3721-10insCCCCCCACCCCCCCCCCCCCC

Variant summary

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

The NM_017570.5(OPLAH):​c.3721-11_3721-10insCCCCCCACCCCCCCCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 257,146 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: OPLAH NM_017570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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 0 ACMG points.

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.3721-11_3721-10insCCCCCCACCCCCCCCCCCCCC		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.3721-11_3721-10insCCCCCCACCCCCCCCCCCCCC		intron	N/A	ENSP00000480476.1	O14841
	OPLAH	ENST00000894965.1		c.3751-11_3751-10insCCCCCCACCCCCCCCCCCCCC		intron	N/A	ENSP00000565024.1
	OPLAH	ENST00000919620.1		c.3745-11_3745-10insCCCCCCACCCCCCCCCCCCCC		intron	N/A	ENSP00000589679.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000389 AC: 1 AN: 257146 Hom.: 0 Cov.: 27 AF XY: 0.00000758 AC XY: 1 AN XY: 131920

⚠️ 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: 5554

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4866

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 18444

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 816

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 186092

Other (OTH) AF: 0.0000846 AC: 1 AN: 11816

⚠️ 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		-1.2

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;