17-58930767-A-G

Variant names:

• chr17-58930767-A-G
• rs7221274
• NM_014906.5:c.465-24882A>G

Variant summary

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

The NM_014906.5(PPM1E):​c.465-24882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,980 control chromosomes in the GnomAD database, including 11,053 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 0.38 (11053 hom., cov: 31)
• Consequence: PPM1E NM_014906.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 10 publications found

Genes affected

PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014906.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	NM_014906.5	MANE Select	c.465-24882A>G		intron	N/A	NP_055721.3
	PPM1E	NR_048561.1		n.594-24882A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	ENST00000308249.4	TSL:1 MANE Select	c.465-24882A>G		intron	N/A	ENSP00000312411.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57356 AN: 151862 Hom.: 11051 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.378 AC: 57378 AN: 151980 Hom.: 11053 Cov.: 31 AF XY: 0.375 AC XY: 27894 AN XY: 74292

African (AFR) AF: 0.366 AC: 15174 AN: 41436

American (AMR) AF: 0.304 AC: 4642 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1692 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1604 AN: 5172

South Asian (SAS) AF: 0.430 AC: 2078 AN: 4828

European-Finnish (FIN) AF: 0.362 AC: 3820 AN: 10542

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27117 AN: 67958

Other (OTH) AF: 0.409 AC: 862 AN: 2106

Alfa AF: 0.393 Hom.: 38118

Bravo AF: 0.371

Asia WGS AF: 0.367 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.54
PhyloP100		0.20
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: rs7221274; hg19: chr17-57008128;