9-111570119-A-G

Position:

• chr9-111570119-A-G

Variant summary

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

The NM_001146108.2(PTGR1):​c.851T>C​(p.Leu284Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGR1 NM_001146108.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

Genes affected

PTGR1 (HGNC:18429): (prostaglandin reductase 1) This gene encodes an enzyme that is involved in the inactivation of the chemotactic factor, leukotriene B4. The encoded protein specifically catalyzes the NADP+ dependent conversion of leukotriene B4 to 12-oxo-leukotriene B4. A pseudogene of this gene is found on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGR1	NM_001146108.2	c.851T>C	p.Leu284Pro	missense_variant	9/10	ENST00000407693.7	NP_001139580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGR1	ENST00000407693.7	c.851T>C	p.Leu284Pro	missense_variant	9/10	1	NM_001146108.2	ENSP00000385763.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.851T>C (p.L284P) alteration is located in exon 9 (coding exon 8) of the PTGR1 gene. This alteration results from a T to C substitution at nucleotide position 851, causing the leucine (L) at amino acid position 284 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.70
MutPred		0.84		Loss of stability (P = 0.0077);Loss of stability (P = 0.0077);Loss of stability (P = 0.0077);
MVP		0.50
MPC		0.61
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.94
gMVP		0.97

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: chr9-114332399;