17-42980063-C-T

Variant names:

• chr17-42980063-C-T
• rs374042386
• NM_001261430.2:c.-10G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001261430.2(PTGES3L):​c.-10G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,551,044 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (26 hom.)
• Consequence: PTGES3L NM_001261430.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.807
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.131).
• BP6: Variant 17-42980063-C-T is Benign according to our data. Variant chr17-42980063-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGES3L	NM_001261430.2	c.-10G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000591916.7	NP_001248359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGES3L	ENST00000591916.7	c.-10G>A		5_prime_UTR_variant	Exon 1 of 7	3	NM_001261430.2	ENSP00000467778.2
PTGES3L-AARSD1	ENST00000421990.7	c.-10G>A		5_prime_UTR_variant	Exon 1 of 17	2		ENSP00000409924.2

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 608 AN: 152186 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00532 AC: 815 AN: 153158 AF XY: 0.00511

Gnomad AFR exome AF: 0.000637

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.0352

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00372

Gnomad NFE exome AF: 0.00525

Gnomad OTH exome AF: 0.00648

GnomAD4 exome AF: 0.00449 AC: 6285 AN: 1398740 Hom.: 26 Cov.: 31 AF XY: 0.00453 AC XY: 3122 AN XY: 689854

African (AFR) AF: 0.000665 AC: 21 AN: 31586

American (AMR) AF: 0.00225 AC: 80 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 905 AN: 25162

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35736

South Asian (SAS) AF: 0.00309 AC: 245 AN: 79218

European-Finnish (FIN) AF: 0.00371 AC: 182 AN: 49062

Middle Eastern (MID) AF: 0.00661 AC: 37 AN: 5594

European-Non Finnish (NFE) AF: 0.00417 AC: 4502 AN: 1078804

Other (OTH) AF: 0.00538 AC: 312 AN: 57950

GnomAD4 genome AF: 0.00399 AC: 607 AN: 152304 Hom.: 4 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74462

African (AFR) AF: 0.000457 AC: 19 AN: 41568

American (AMR) AF: 0.00190 AC: 29 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00554 AC: 377 AN: 68016

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00771 Hom.: 4

Bravo AF: 0.00357

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PTGES3L-AARSD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		-0.81
PromoterAI		-0.014	Neutral

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: rs374042386; hg19: chr17-41132080; COSMIC: COSV100799216; COSMIC: COSV100799216;