17-42969192-GGC-GGCGC

Variant names:

• chr17-42969192-G-GGC
• rs200141347
• NM_001261430.2:c.433-8_433-7dupGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001261430.2(PTGES3L):​c.433-8_433-7dupGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 21)
• Consequence: PTGES3L NM_001261430.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 2 publications found

Genes affected

PTGES3L (HGNC:43943): (prostaglandin E synthase 3 like) Predicted to enable Hsp90 protein binding activity and chaperone binding activity. Predicted to be involved in chaperone-mediated protein complex assembly and protein folding. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PTGES3L-AARSD1 (HGNC:43946): (PTGES3L-AARSD1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring PTGES3L (prostaglandin E synthase 3 (cytosolic)-like) and AARSD1(alanyl-tRNA synthetase domain containing 1) genes on chromosome 17. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, May 2012]

ENSG00000308697 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261430.2. 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
	PTGES3L	NM_001261430.2	MANE Select	c.433-8_433-7dupGC		splice_region intron	N/A	NP_001248359.2
	PTGES3L-AARSD1	NM_001136042.2		c.561+1095_561+1096dupGC		intron	N/A	NP_001129514.2
	PTGES3L-AARSD1	NM_025267.4		c.378+1095_378+1096dupGC		intron	N/A	NP_079543.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3L	ENST00000591916.7	TSL:3 MANE Select	c.433-7_433-6insGC		splice_region intron	N/A	ENSP00000467778.2
	PTGES3L-AARSD1	ENST00000421990.7	TSL:2	c.432+1096_432+1097insGC		intron	N/A	ENSP00000409924.2
	PTGES3L-AARSD1	ENST00000409399.6	TSL:5	c.432+1096_432+1097insGC		intron	N/A	ENSP00000386621.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs200141347; hg19: chr17-41121209;