17-58973004-C-T

Position:

• chr17-58973004-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014906.5(PPM1E):​c.1210+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 891,708 control chromosomes in the GnomAD database, including 17,836 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 0.18 (2738 hom., cov: 32)
  • Exomes 𝑓: 0.19 (15098 hom.)
• Consequence: PPM1E NM_014906.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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]

TRIM37 (HGNC:7523): (tripartite motif containing 37) This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein-protein and/or protein-nucleic acid interactions. Mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. TRIM37 localizes in peroxisomal membranes, and has been implicated in human peroxisomal biogenesis disorders. [provided by RefSeq, Jul 2020]

PPM1E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1E	NM_014906.5	c.1210+79C>T		intron_variant		ENST00000308249.4	NP_055721.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1E	ENST00000308249.4	c.1210+79C>T		intron_variant		1	NM_014906.5	ENSP00000312411.2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27971 AN: 151964 Hom.: 2735 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.195 AC: 144103 AN: 739626 Hom.: 15098 AF XY: 0.192 AC XY: 74150 AN XY: 386358

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.0851

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.184 AC: 27989 AN: 152082 Hom.: 2738 Cov.: 32 AF XY: 0.187 AC XY: 13889 AN XY: 74334

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.165

Alfa AF: 0.192 Hom.: 5815

Bravo AF: 0.170

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.9
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs16943326; hg19: chr17-57050365;