Genetic Variant PTGES3L:c.-10G>A (chr17-42980063-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001136042.2(PTGES3L-AARSD1):c.120G>A(p.Ala40Ala) variant causes a synonymous 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-AARSD1
NM_001136042.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.807

Variant links:

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 links:

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]

PTGES3L-AARSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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.

BP7

Synonymous conserved (PhyloP=-0.807 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGES3L	NM_001261430.2 link	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 link	c.-10G>A		5_prime_UTR_variant	Exon 1 of 7	3	NM_001261430.2	ENSP00000467778.2		H7C1Q7
PTGES3L-AARSD1	ENST00000421990.7 link	c.-10G>A		5_prime_UTR_variant	Exon 1 of 17	2		ENSP00000409924.2		B3KSP9

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

608

AN:

152186

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00532

AC:

815

AN:

153158

Hom.:

AF XY:

0.00511

AC XY:

416

AN XY:

81334

show subpopulations

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 SAS exome

AF:

0.00312

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.:

Cov.:

AF XY:

0.00453

AC XY:

3122

AN XY:

689854

show subpopulations

Gnomad4 AFR exome

AF:

0.000665

Gnomad4 AMR exome

AF:

0.00225

Gnomad4 ASJ exome

AF:

0.0360

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00417

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.00399

AC:

607

AN:

152304

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over