8-144051482-CGGGGGG-CGGGGGGGG

Variant names:

• chr8-144051482-C-CGG
• rs782568024
• NM_017570.5:c.3721-12_3721-11dupCC

Variant summary

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

The NM_017570.5(OPLAH):​c.3721-12_3721-11dupCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 254,434 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: 𝑓 0.0021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0021 (0 hom.)
  • Failed GnomAD Quality Control
• 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.3721-12_3721-11dupCC		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.3721-12_3721-11dupCC		intron	N/A	ENSP00000480476.1	O14841
	OPLAH	ENST00000894965.1		c.3751-12_3751-11dupCC		intron	N/A	ENSP00000565024.1
	OPLAH	ENST00000919620.1		c.3745-12_3745-11dupCC		intron	N/A	ENSP00000589679.1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 48 AN: 22832 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00194

Gnomad ASJ AF: 0.00200

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00338

GnomAD2 exomes AF: 0.000812 AC: 26 AN: 32016 AF XY: 0.000544

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000331

Gnomad FIN exome AF: 0.000486

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00207 AC: 527 AN: 254434 Hom.: 0 Cov.: 27 AF XY: 0.00202 AC XY: 263 AN XY: 130502

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

African (AFR) AF: 0.00346 AC: 19 AN: 5498

American (AMR) AF: 0.00229 AC: 20 AN: 8738

Ashkenazi Jewish (ASJ) AF: 0.00460 AC: 22 AN: 4780

East Asian (EAS) AF: 0.0000983 AC: 1 AN: 10178

South Asian (SAS) AF: 0.00433 AC: 78 AN: 18018

European-Finnish (FIN) AF: 0.00134 AC: 14 AN: 10434

Middle Eastern (MID) AF: 0.00247 AC: 2 AN: 810

European-Non Finnish (NFE) AF: 0.00191 AC: 352 AN: 184306

Other (OTH) AF: 0.00163 AC: 19 AN: 11672

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00210 AC: 48 AN: 22846 Hom.: 0 Cov.: 29 AF XY: 0.00205 AC XY: 23 AN XY: 11210

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

African (AFR) AF: 0.00222 AC: 11 AN: 4964

American (AMR) AF: 0.00193 AC: 4 AN: 2068

Ashkenazi Jewish (ASJ) AF: 0.00200 AC: 1 AN: 500

East Asian (EAS) AF: 0.00111 AC: 1 AN: 902

South Asian (SAS) AF: 0.0127 AC: 8 AN: 628

European-Finnish (FIN) AF: 0.00387 AC: 4 AN: 1034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00147 AC: 18 AN: 12258

Other (OTH) AF: 0.00338 AC: 1 AN: 296

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000112 Hom.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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;