12-79690120-G-C

Variant names:

• chr12-79690120-G-C
• NM_002583.4:c.125C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002583.4(PAWR):​c.125C>G​(p.Pro42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAWR NM_002583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1559313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAWR	NM_002583.4	c.125C>G	p.Pro42Arg	missense_variant	Exon 2 of 7	ENST00000328827.9	NP_002574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAWR	ENST00000328827.9	c.125C>G	p.Pro42Arg	missense_variant	Exon 2 of 7	1	NM_002583.4	ENSP00000328088.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1335048 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 659090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.27	T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.45	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.30	N;N;N
REVEL	Benign	0.016
Sift	Benign	0.10	T;D;D
Sift4G	Benign	0.17	T;.;.
Polyphen		0.60	P;.;.
Vest4		0.093
MutPred		0.26		Gain of catalytic residue at G43 (P = 0.0024);Gain of catalytic residue at G43 (P = 0.0024);Gain of catalytic residue at G43 (P = 0.0024);
MVP		0.42
MPC		0.50
ClinPred		0.31	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-80083900;