rs200141347

Positions:

• chr17-42969192-GGC-G
• chr17-42969192-GGC-GGCGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001261430.2(PTGES3L):​c.433-8_433-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 727,068 control chromosomes in the GnomAD database, including 192 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (78 hom., cov: 0)
  • Exomes 𝑓: 0.032 (114 hom.)
• Consequence: PTGES3L NM_001261430.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.192

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-42969192-GGC-G is Benign according to our data. Variant chr17-42969192-GGC-G is described in ClinVar as [Benign]. Clinvar id is 403353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGES3L	NM_001261430.2	c.433-8_433-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000591916.7
PTGES3L-AARSD1	NM_001136042.2	c.561+1095_561+1096del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGES3L	ENST00000591916.7	c.433-8_433-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3	NM_001261430.2	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 2606 AN: 16442 Hom.: 78 Cov.: 0

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.00538

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.0319 AC: 22641 AN: 710560 Hom.: 114 AF XY: 0.0330 AC XY: 11425 AN XY: 346558

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0295

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.0571

Gnomad4 SAS exome AF: 0.0744

Gnomad4 FIN exome AF: 0.0340

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.0375

GnomAD4 genome AF: 0.159 AC: 2618 AN: 16508 Hom.: 78 Cov.: 0 AF XY: 0.159 AC XY: 1299 AN XY: 8156

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.00538

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.136

Alfa AF: 0.287 Hom.: 427

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200141347; hg19: chr17-41121209;