NM_021222.3:c.3_7dupGGAGG

Variant names:

• chr1-151008634-T-TGGAGG
• rs1553251507
• NM_021222.3:c.3_7dupGGAGG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_021222.3(PRUNE1):​c.3_7dupGGAGG​(p.Asp3GlyfsTer42) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRUNE1 NM_021222.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.41
• Publications: 0 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]

MINDY1 (HGNC:25648): (MINDY lysine 48 deubiquitinase 1) Enables K48-linked polyubiquitin modification-dependent protein binding activity; Lys48-specific deubiquitinase activity; and cysteine-type carboxypeptidase activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 22 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-151008634-T-TGGAGG is Pathogenic according to our data. Variant chr1-151008634-T-TGGAGG is described in ClinVar as Pathogenic. ClinVar VariationId is 521739.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3_7dupGGAGG	p.Asp3GlyfsTer42	frameshift	Exon 1 of 8	NP_067045.1
	PRUNE1	NM_001303242.2		c.3_7dupGGAGG	p.Asp3GlyfsTer42	frameshift	Exon 1 of 7	NP_001290171.1
	PRUNE1	NM_001303229.2		c.-341_-337dupGGAGG		5_prime_UTR	Exon 1 of 7	NP_001290158.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE1	ENST00000271620.8	TSL:1 MANE Select	c.3_7dupGGAGG	p.Asp3GlyfsTer42	frameshift	Exon 1 of 8	ENSP00000271620.3
	PRUNE1	ENST00000368936.5	TSL:1	c.-341_-337dupGGAGG		5_prime_UTR	Exon 1 of 7	ENSP00000357932.1
	PRUNE1	ENST00000368937.5	TSL:1	c.-63_-59dupGGAGG		5_prime_UTR	Exon 1 of 4	ENSP00000357933.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4
Mutation Taster		=14/186	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553251507; hg19: chr1-150981110;