NM_002583.4:c.299_300delGGinsAA

Variant names:

• chr12-79689945-CC-TT
• NM_002583.4:c.299_300delGGinsAA
• PAWR p.Arg100Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002583.4(PAWR):​c.299_300delGGinsAA​(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAWR NM_002583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 0 publications found

Genes affected

PAWR (HGNC:8614): (pro-apoptotic WT1 regulator) This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]

PPP1R12A-AS2 (HGNC:55456): (PPP1R12A antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002583.4. 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
	PAWR	NM_002583.4	MANE Select	c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	NP_002574.2	Q96IZ0
	PAWR	NM_001354732.2		c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	NP_001341661.1	Q96IZ0
	PAWR	NM_001354733.2		c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	NP_001341662.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	ENST00000328827.9	TSL:1 MANE Select	c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	ENSP00000328088.4	Q96IZ0
	PAWR	ENST00000903360.1		c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	ENSP00000573419.1
	PAWR	ENST00000912080.1		c.299_300delGGinsAA	p.Arg100Gln	missense	N/A	ENSP00000582139.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-80083725;