rs2958154

Variant names:

• chr12-56671929-C-G
• rs2958154
• NM_006601.7:c.187-82G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-56671929-C-G
• chr12-56671929-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006601.7(PTGES3):​c.187-82G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 684,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PTGES3 NM_006601.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 32 publications found

Genes affected

PTGES3 (HGNC:16049): (prostaglandin E synthase 3) This gene encodes an enzyme that converts prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). This protein functions as a co-chaperone with heat shock protein 90 (HSP90), localizing to response elements in DNA and disrupting transcriptional activation complexes. Alternative splicing results in multiple transcript variants. There are multiple pseudogenes of this gene on several different chromosomes. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006601.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3	NM_006601.7	MANE Select	c.187-82G>C		intron	N/A	NP_006592.3
	PTGES3	NM_001282604.2		c.199-82G>C		intron	N/A	NP_001269533.1
	PTGES3	NM_001282601.2		c.187-82G>C		intron	N/A	NP_001269530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3	ENST00000262033.11	TSL:1 MANE Select	c.187-82G>C		intron	N/A	ENSP00000262033.6
	PTGES3	ENST00000456859.2	TSL:2	c.117-120G>C		intron	N/A	ENSP00000389090.2
	PTGES3	ENST00000614328.4	TSL:3	c.199-82G>C		intron	N/A	ENSP00000482075.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000146 AC: 1 AN: 684736 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 343028

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

African (AFR) AF: 0.00 AC: 0 AN: 15026

American (AMR) AF: 0.00 AC: 0 AN: 13710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13454

East Asian (EAS) AF: 0.00 AC: 0 AN: 27746

South Asian (SAS) AF: 0.00 AC: 0 AN: 25738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3776

European-Non Finnish (NFE) AF: 0.00000195 AC: 1 AN: 513524

Other (OTH) AF: 0.00 AC: 0 AN: 30580

⚠️ 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.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-2.3

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: rs2958154; hg19: chr12-57065713;