NM_021222.3:c.133-30G>C

Variant names:

• chr1-151018437-G-C
• rs7526955
• NM_021222.3:c.133-30G>C

Variant summary

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

The NM_021222.3(PRUNE1):​c.133-30G>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
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 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.133-30G>C		intron	N/A	NP_067045.1	Q86TP1-1
	PRUNE1	NM_001303242.2		c.133-30G>C		intron	N/A	NP_001290171.1
	PRUNE1	NM_001303229.2		c.-212+533G>C		intron	N/A	NP_001290158.1	Q86TP1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	ENST00000271620.8	TSL:1 MANE Select	c.133-30G>C		intron	N/A	ENSP00000271620.3	Q86TP1-1
	PRUNE1	ENST00000368936.5	TSL:1	c.-212+533G>C		intron	N/A	ENSP00000357932.1	Q86TP1-3
	PRUNE1	ENST00000368937.5	TSL:1	c.-26-7078G>C		intron	N/A	ENSP00000357933.1	Q86TP1-5

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

GnomAD2 exomes AF: 0.0584 AC: 14583 AN: 249736 AF XY: 0.0553

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 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

African (AFR) AF: 0.163 AC: 5246 AN: 32210

American (AMR) AF: 0.0312 AC: 1391 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 1591 AN: 25826

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39402

South Asian (SAS) AF: 0.0144 AC: 1225 AN: 85080

European-Finnish (FIN) AF: 0.0644 AC: 3354 AN: 52092

Middle Eastern (MID) AF: 0.0401 AC: 227 AN: 5664

European-Non Finnish (NFE) AF: 0.0776 AC: 82440 AN: 1062798

Other (OTH) AF: 0.0722 AC: 4226 AN: 58560

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

African (AFR) AF: 0.155 AC: 6433 AN: 41490

American (AMR) AF: 0.0509 AC: 777 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4826

European-Finnish (FIN) AF: 0.0720 AC: 762 AN: 10586

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0751 AC: 5105 AN: 67994

Other (OTH) AF: 0.0773 AC: 163 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.39
PhyloP100		-0.089
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: rs7526955; hg19: chr1-150990913;