chr9-111578867-T-C

Variant names:

• chr9-111578867-T-C
• rs141717707
• NM_001146108.2:c.580A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001146108.2(PTGR1):​c.580A>G​(p.Lys194Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: PTGR1 NM_001146108.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.47
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146108.2. 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
	PTGR1	NM_001146108.2	MANE Select	c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	NP_001139580.1	Q14914-1
	PTGR1	NM_012212.3		c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	NP_036344.2	Q14914-1
	PTGR1	NM_001146109.2		c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	NP_001139581.1	Q14914-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGR1	ENST00000407693.7	TSL:1 MANE Select	c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	ENSP00000385763.2	Q14914-1
	PTGR1	ENST00000309195.9	TSL:1	c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	ENSP00000311572.5	Q14914-1
	PTGR1	ENST00000878676.1		c.580A>G	p.Lys194Glu	missense	Exon 7 of 10	ENSP00000548735.1

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151652 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.0000950

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251190 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000787 AC: 115 AN: 1461464 Hom.: 0 Cov.: 30 AF XY: 0.0000839 AC XY: 61 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000971 AC: 108 AN: 1111684

Other (OTH) AF: 0.0000331 AC: 2 AN: 60368

GnomAD4 genome AF: 0.0000725 AC: 11 AN: 151652 Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2 AN XY: 74036

African (AFR) AF: 0.00 AC: 0 AN: 41236

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.0000950 AC: 1 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000154 Hom.: 2

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.85
MVP		0.69
MPC		0.58
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.87
gMVP		0.81
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs141717707; hg19: chr9-114341147;