rs3738479

Variant names:

• chr1-151025366-T-A
• rs3738479
• NM_021222.3:c.521-149T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021222.3(PRUNE1):​c.521-149T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 723,754 control chromosomes in the GnomAD database, including 25,910 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 0.29 (7134 hom., cov: 31)
  • Exomes 𝑓: 0.25 (18776 hom.)
• Consequence: PRUNE1 NM_021222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 5 publications found

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]

PRUNE1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021222.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	NM_021222.3	MANE Select	c.521-149T>A		intron	N/A	NP_067045.1
	PRUNE1	NM_001303242.2		c.521-149T>A		intron	N/A	NP_001290171.1
	PRUNE1	NM_001303229.2		c.-26-149T>A		intron	N/A	NP_001290158.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	ENST00000271620.8	TSL:1 MANE Select	c.521-149T>A		intron	N/A	ENSP00000271620.3
	PRUNE1	ENST00000368936.5	TSL:1	c.-26-149T>A		intron	N/A	ENSP00000357932.1
	PRUNE1	ENST00000368937.5	TSL:1	c.-26-149T>A		intron	N/A	ENSP00000357933.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44490 AN: 151926 Hom.: 7125 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.245 AC: 140341 AN: 571710 Hom.: 18776 AF XY: 0.246 AC XY: 71360 AN XY: 289630

African (AFR) AF: 0.387 AC: 5089 AN: 13138

American (AMR) AF: 0.297 AC: 4039 AN: 13596

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 2405 AN: 12724

East Asian (EAS) AF: 0.405 AC: 11265 AN: 27802

South Asian (SAS) AF: 0.348 AC: 10966 AN: 31502

European-Finnish (FIN) AF: 0.230 AC: 9036 AN: 39300

Middle Eastern (MID) AF: 0.232 AC: 506 AN: 2182

European-Non Finnish (NFE) AF: 0.223 AC: 89949 AN: 403094

Other (OTH) AF: 0.250 AC: 7086 AN: 28372

GnomAD4 genome AF: 0.293 AC: 44537 AN: 152044 Hom.: 7134 Cov.: 31 AF XY: 0.294 AC XY: 21868 AN XY: 74302

African (AFR) AF: 0.394 AC: 16318 AN: 41458

American (AMR) AF: 0.286 AC: 4368 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2575 AN: 5160

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4814

European-Finnish (FIN) AF: 0.229 AC: 2427 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15556 AN: 67978

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.261 Hom.: 708

Bravo AF: 0.303

Asia WGS AF: 0.404 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3738479; hg19: chr1-150997842;