17-42967552-T-G

Variant names:

• chr17-42967552-T-G
• rs188757965
• ENST00000421990.7:c.432+2737A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000421990.7(PTGES3L-AARSD1):​c.432+2737A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: PTGES3L-AARSD1 ENST00000421990.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 4 publications found

Genes affected

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421990.7. 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-AARSD1	NM_001136042.2		c.561+2737A>C		intron	N/A	NP_001129514.2
	PTGES3L-AARSD1	NM_025267.4		c.378+2737A>C		intron	N/A	NP_079543.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3L-AARSD1	ENST00000421990.7	TSL:2	c.432+2737A>C		intron	N/A	ENSP00000409924.2
	PTGES3L-AARSD1	ENST00000409399.6	TSL:5	c.432+2737A>C		intron	N/A	ENSP00000386621.2
	PTGES3L-AARSD1	ENST00000360221.8	TSL:2	c.378+2737A>C		intron	N/A	ENSP00000353355.4

Frequencies

GnomAD3 genomes AF: 0.0000801 AC: 11 AN: 137400 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000814

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000873 AC: 12 AN: 137394 Hom.: 0 Cov.: 29 AF XY: 0.000122 AC XY: 8 AN XY: 65632

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

African (AFR) AF: 0.000302 AC: 11 AN: 36448

American (AMR) AF: 0.0000813 AC: 1 AN: 12302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65902

Other (OTH) AF: 0.00 AC: 0 AN: 1882

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00269693), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000165 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.17
PhyloP100		0.17

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: rs188757965; hg19: chr17-41119569;