rs381523

Variant names:

• chr22-21951257-A-C
• rs381523
• NM_014634.4:c.-61+1535T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-21951257-A-C
• chr22-21951257-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014634.4(PPM1F):​c.-61+1535T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: PPM1F NM_014634.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 publications found

Genes affected

PPM1F (HGNC:19388): (protein phosphatase, Mg2+/Mn2+ dependent 1F) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PPM1F-AS1 (HGNC:40888): (PPM1F antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014634.4. 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
	PPM1F	NM_014634.4	MANE Select	c.-61+1535T>G		intron	N/A	NP_055449.1	P49593-1
	PPM1F	NM_001410836.1		c.-299+1535T>G		intron	N/A	NP_001397765.1	B5MCT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1F	ENST00000263212.10	TSL:1 MANE Select	c.-61+1535T>G		intron	N/A	ENSP00000263212.5	P49593-1
	PPM1F-AS1	ENST00000458178.2	TSL:1	n.11477A>C		non_coding_transcript_exon	Exon 2 of 2
	PPM1F	ENST00000397495.8	TSL:2	c.-61+1535T>G		intron	N/A	ENSP00000380632.4	A8MX49

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.47
PhyloP100		-1.1

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: rs381523; hg19: chr22-22305629;