Genetic Variant OPLAH:c.3721-11_3721-10insCCCCCCCCCCCCCCC (chr8-144051482-C-CGGGGGGGGGGGGGGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_017570.5(OPLAH):c.3721-11_3721-10insCCCCCCCCCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000713 in 280,354 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: 𝑓 0.000043 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

OPLAH
NM_017570.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

0 publications found

Variant links:

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)

OPLAH links:

ENSG00000293498 (HGNC:):

ENSG00000293498 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_3721-10insCCCCCCCCCCCCCCC		intron	N/A	NP_060040.1	O14841

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPLAH	ENST00000618853.5	TSL:1 MANE Select	c.3721-11_3721-10insCCCCCCCCCCCCCCC	intron	N/A	ENSP00000480476.1	O14841
OPLAH	ENST00000894965.1		c.3751-11_3751-10insCCCCCCCCCCCCCCC	intron	N/A	ENSP00000565024.1
OPLAH	ENST00000919620.1		c.3745-11_3745-10insCCCCCCCCCCCCCCC	intron	N/A	ENSP00000589679.1

Frequencies

GnomAD3 genomes

AF:

0.0000429

AC:

AN:

23304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000389

AC:

AN:

257050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

131864

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

5554

American (AMR)

AF:

0.00

AC:

AN:

8834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4866

East Asian (EAS)

AF:

0.00

AC:

AN:

10202

South Asian (SAS)

AF:

0.00

AC:

AN:

18440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

816

European-Non Finnish (NFE)

AF:

0.00000538

AC:

AN:

186004

Other (OTH)

AF:

0.00

AC:

AN:

11814

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000429

AC:

AN:

23304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11392

show subpopulations

African (AFR)

AF:

0.000200

AC:

AN:

5008

American (AMR)

AF:

0.00

AC:

AN:

2092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

522

East Asian (EAS)

AF:

0.00

AC:

AN:

908

South Asian (SAS)

AF:

0.00

AC:

AN:

644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

12574

Other (OTH)

AF:

0.00

AC:

AN:

308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Publications

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8-144051482-CGGGGGG-CGGGGGGGGGGGGGGGGGGGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over