rs7526955

chr1-151018437-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021222.3(PRUNE1):c.133-30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,558,364 control chromosomes in the GnomAD database, including 4,764 homozygotes. 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 0.089 (752 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4012 hom.)
• Consequence: PRUNE1 NM_021222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

Genes affected

PRUNE1 (HGNC:13420): (prune exopolyphosphatase 1) This gene encodes a member of the DHH protein superfamily of phosphoesterases. This protein has been found to function as both a nucleotide phosphodiesterase and an exopolyphosphatase. This protein is believed to stimulate cancer progression and metastases through the induction of cell motility. A pseuodgene has been identified on chromosome 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRUNE1	NM_021222.3	c.133-30G>C		intron_variant		ENST00000271620.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRUNE1	ENST00000271620.8	c.133-30G>C		intron_variant		1	NM_021222.3	P1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13543 AN: 152014 Hom.: 753 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0781

GnomAD3 exomes AF: 0.0584 AC: 14583 AN: 249736 Hom.: 560 AF XY: 0.0553 AC XY: 7473 AN XY: 135212

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0287

Gnomad ASJ exome AF: 0.0605

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0129

Gnomad FIN exome AF: 0.0694

Gnomad NFE exome AF: 0.0727

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0709 AC: 99701 AN: 1406232 Hom.: 4012 Cov.: 28 AF XY: 0.0688 AC XY: 48368 AN XY: 702802

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0312

Gnomad4 ASJ exome AF: 0.0616

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.0776

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0891 AC: 13556 AN: 152132 Hom.: 752 Cov.: 32 AF XY: 0.0864 AC XY: 6424 AN XY: 74382

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0787 Hom.: 105

Bravo AF: 0.0897

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.7
Dann	Benign	0.39

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

Other links and lift over

dbSNP: rs7526955; hg19: chr1-150990913;