chr17-42980063-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001261430.2(PTGES3L):​c.-10G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,398,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PTGES3L NM_001261430.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGES3L	NM_001261430.2	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000591916.7	NP_001248359.2
PTGES3L	NM_001261430.2	c.-10G>T		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>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	3	NM_001261430.2	ENSP00000467778.2
PTGES3L-AARSD1	ENST00000421990.7	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	2		ENSP00000409924.2
PTGES3L	ENST00000591916.7	c.-10G>T		5_prime_UTR_variant	Exon 1 of 7	3	NM_001261430.2	ENSP00000467778.2
PTGES3L-AARSD1	ENST00000421990.7	c.-10G>T		5_prime_UTR_variant	Exon 1 of 17	2		ENSP00000409924.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000114 AC: 16 AN: 1398746 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 689856

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.0000148 AC: 16 AN: 1078808

Other (OTH) AF: 0.00 AC: 0 AN: 57950

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		-0.81
PromoterAI		0.034	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;