8-144051477-TGGCGCGGGGG-T

Variant names:

• chr8-144051477-TGGCGCGGGGG-T
• NM_017570.5:c.3721-15_3721-6delCCCCCGCGCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_017570.5(OPLAH):​c.3721-15_3721-6delCCCCCGCGCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OPLAH NM_017570.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.249

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]

SMPD5 (HGNC:52275): (sphingomyelin phosphodiesterase 5 (pseudogene)) Predicted to enable sphingomyelin phosphodiesterase activity. Predicted to be involved in ceramide biosynthetic process and sphingomyelin catabolic process. Predicted to act upstream of or within ceramide metabolic process. Predicted to be located in endoplasmic reticulum membrane and mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 8-144051477-TGGCGCGGGGG-T is Benign according to our data. Variant chr8-144051477-TGGCGCGGGGG-T is described in ClinVar as [Likely_benign]. Clinvar id is 3635942.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPLAH	NM_017570.5	c.3721-15_3721-6delCCCCCGCGCC		splice_region_variant, intron_variant	Intron 26 of 26	ENST00000618853.5	NP_060040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5	c.3721-15_3721-6delCCCCCGCGCC		splice_region_variant, intron_variant	Intron 26 of 26	1	NM_017570.5	ENSP00000480476.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 282046 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 142108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

5-Oxoprolinase deficiency Benign:1

Jun 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145106378;