rs11777194

Variant names:

• chr8-144054850-C-G
• NM_017570.5:c.2473G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144054850-C-G
• chr8-144054850-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017570.5(OPLAH):​c.2473G>C​(p.Gly825Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OPLAH NM_017570.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPLAH	NM_017570.5	c.2473G>C	p.Gly825Arg	missense_variant	Exon 18 of 27	ENST00000618853.5	NP_060040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPLAH	ENST00000618853.5	c.2473G>C	p.Gly825Arg	missense_variant	Exon 18 of 27	1	NM_017570.5	ENSP00000480476.1
OPLAH	ENST00000531027.1	n.30G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
OPLAH	ENST00000527993.1	n.-197G>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459986 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.61
CADD	Pathogenic	26
DANN	Benign	0.92
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.015	T
PrimateAI	Uncertain	0.77	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.87		Gain of solvent accessibility (P = 1e-04);
MVP		0.32
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.93
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr8-145109753;