rs4970989

Variant names:

• chr1-151031124-T-A
• rs4970989
• NM_021222.3:c.933+2180T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151031124-T-A
• chr1-151031124-T-C
• chr1-151031124-T-G

Variant summary

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

The NM_021222.3(PRUNE1):​c.933+2180T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 150,876 control chromosomes in the GnomAD database, including 36,910 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 0.68 (36910 hom., cov: 27)
• Consequence: PRUNE1 NM_021222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 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.933+2180T>A		intron	N/A	NP_067045.1
	PRUNE1	NM_001303242.2		c.775-2682T>A		intron	N/A	NP_001290171.1
	PRUNE1	NM_001303229.2		c.387+2180T>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.933+2180T>A		intron	N/A	ENSP00000271620.3
	PRUNE1	ENST00000368936.5	TSL:1	c.387+2180T>A		intron	N/A	ENSP00000357932.1
	PRUNE1	ENST00000368937.5	TSL:1	c.229-2682T>A		intron	N/A	ENSP00000357933.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102159 AN: 150768 Hom.: 36914 Cov.: 27

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.677 AC: 102181 AN: 150876 Hom.: 36910 Cov.: 27 AF XY: 0.680 AC XY: 50051 AN XY: 73558

African (AFR) AF: 0.394 AC: 16194 AN: 41074

American (AMR) AF: 0.763 AC: 11516 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2758 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4500 AN: 5116

South Asian (SAS) AF: 0.785 AC: 3761 AN: 4794

European-Finnish (FIN) AF: 0.752 AC: 7624 AN: 10132

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53341 AN: 67898

Other (OTH) AF: 0.724 AC: 1518 AN: 2096

Alfa AF: 0.713 Hom.: 4995

Bravo AF: 0.669

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		0.13
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: rs4970989; hg19: chr1-151003600;