rs3738480

Variant names:

• chr1-151018349-A-G
• rs3738480
• NM_021222.3:c.133-118A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-151018349-A-G
• chr1-151018349-A-T

Variant summary

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

The NM_021222.3(PRUNE1):​c.133-118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 890,738 control chromosomes in the GnomAD database, including 254,625 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 0.73 (41147 hom., cov: 31)
  • Exomes 𝑓: 0.76 (213478 hom.)
• Consequence: PRUNE1 NM_021222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	NM_021222.3	MANE Select	c.133-118A>G		intron	N/A	NP_067045.1
	PRUNE1	NM_001303242.2		c.133-118A>G		intron	N/A	NP_001290171.1
	PRUNE1	NM_001303229.2		c.-212+445A>G		intron	N/A	NP_001290158.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	ENST00000271620.8	TSL:1 MANE Select	c.133-118A>G		intron	N/A	ENSP00000271620.3
	PRUNE1	ENST00000368936.5	TSL:1	c.-212+445A>G		intron	N/A	ENSP00000357932.1
	PRUNE1	ENST00000368937.5	TSL:1	c.-26-7166A>G		intron	N/A	ENSP00000357933.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111458 AN: 151850 Hom.: 41118 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.761

GnomAD2 exomes AF: 0.761 AC: 180098 AN: 236714 AF XY: 0.771

Gnomad AFR exome AF: 0.714

Gnomad AMR exome AF: 0.678

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.890

Gnomad FIN exome AF: 0.674

Gnomad NFE exome AF: 0.749

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.758 AC: 559753 AN: 738770 Hom.: 213478 Cov.: 9 AF XY: 0.765 AC XY: 302503 AN XY: 395422

African (AFR) AF: 0.711 AC: 14096 AN: 19812

American (AMR) AF: 0.679 AC: 29758 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 16429 AN: 21728

East Asian (EAS) AF: 0.874 AC: 31896 AN: 36514

South Asian (SAS) AF: 0.881 AC: 62916 AN: 71454

European-Finnish (FIN) AF: 0.676 AC: 27088 AN: 40076

Middle Eastern (MID) AF: 0.869 AC: 2975 AN: 3424

European-Non Finnish (NFE) AF: 0.746 AC: 346785 AN: 464928

Other (OTH) AF: 0.752 AC: 27810 AN: 36990

GnomAD4 genome AF: 0.734 AC: 111546 AN: 151968 Hom.: 41147 Cov.: 31 AF XY: 0.732 AC XY: 54384 AN XY: 74264

African (AFR) AF: 0.714 AC: 29578 AN: 41440

American (AMR) AF: 0.681 AC: 10374 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4573 AN: 5174

South Asian (SAS) AF: 0.880 AC: 4238 AN: 4816

European-Finnish (FIN) AF: 0.660 AC: 6966 AN: 10560

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50587 AN: 67962

Other (OTH) AF: 0.763 AC: 1609 AN: 2110

Alfa AF: 0.745 Hom.: 192033

Bravo AF: 0.733

Asia WGS AF: 0.847 AC: 2946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.51
PhyloP100		-0.49
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: rs3738480; hg19: chr1-150990825;