17-42969192-GGC-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001261430.2(PTGES3L):​c.433-8_433-7delGC variant causes a splice region, 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, 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: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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTGES3L	NM_001261430.2	c.433-8_433-7delGC		splice_region_variant, intron_variant	Intron 6 of 6	ENST00000591916.7	NP_001248359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGES3L	ENST00000591916.7	c.433-8_433-7delGC		splice_region_variant, intron_variant	Intron 6 of 6	3	NM_001261430.2	ENSP00000467778.2
PTGES3L-AARSD1	ENST00000421990.7	c.432+1095_432+1096delGC		intron_variant	Intron 6 of 16	2		ENSP00000409924.2

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

GnomAD2 exomes AF: 0.0332 AC: 2764 AN: 83178 AF XY: 0.0339

Gnomad AFR exome AF: 0.0615

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.0161

Gnomad EAS exome AF: 0.0726

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0269

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

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

African (AFR) AF: 0.122 AC: 1075 AN: 8844

American (AMR) AF: 0.0295 AC: 543 AN: 18438

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 251 AN: 9042

East Asian (EAS) AF: 0.0571 AC: 880 AN: 15418

South Asian (SAS) AF: 0.0744 AC: 2583 AN: 34732

European-Finnish (FIN) AF: 0.0340 AC: 536 AN: 15768

Middle Eastern (MID) AF: 0.0617 AC: 158 AN: 2562

European-Non Finnish (NFE) AF: 0.0270 AC: 15586 AN: 578290

Other (OTH) AF: 0.0375 AC: 1029 AN: 27466

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.204 AC: 1918 AN: 9404

American (AMR) AF: 0.134 AC: 152 AN: 1136

Ashkenazi Jewish (ASJ) AF: 0.00538 AC: 1 AN: 186

East Asian (EAS) AF: 0.0185 AC: 12 AN: 648

South Asian (SAS) AF: 0.240 AC: 136 AN: 566

European-Finnish (FIN) AF: 0.0657 AC: 43 AN: 654

Middle Eastern (MID) AF: 0.262 AC: 11 AN: 42

European-Non Finnish (NFE) AF: 0.0867 AC: 312 AN: 3600

Other (OTH) AF: 0.136 AC: 33 AN: 242

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19

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

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Other links and lift over

dbSNP: rs200141347; hg19: chr17-41121209; COSMIC: COSV64182297; COSMIC: COSV64182297;