3-160882775-A-G

Position:

• chr3-160882775-A-G

Variant summary

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

The NM_139245.4(PPM1L):​c.400-78961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,222 control chromosomes in the GnomAD database, including 5,658 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 0.27 (5658 hom., cov: 32)
• Consequence: PPM1L NM_139245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

PPM1L (HGNC:16381): (protein phosphatase, Mg2+/Mn2+ dependent 1L) The protein encoded by this gene is a magnesium or manganese-requiring phosphatase that is involved in several signaling pathways. The encoded protein downregulates apoptosis signal-regulating kinase 1, a protein that initiates a signaling cascade that leads to apoptosis when cells are subjected to cytotoxic stresses. This protein also is an endoplasmic reticulum transmembrane protein that helps regulate ceramide transport from the endoplasmic reticulum to the Golgi apparatus. Finally, this gene may be involved in adiposity since it is upregulated in adipose tissues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1L	NM_139245.4	c.400-78961A>G		intron_variant		ENST00000498165.6	NP_640338.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1L	ENST00000498165.6	c.400-78961A>G		intron_variant		1	NM_139245.4	ENSP00000417659.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40385 AN: 152104 Hom.: 5660 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.265 AC: 40391 AN: 152222 Hom.: 5658 Cov.: 32 AF XY: 0.269 AC XY: 20018 AN XY: 74414

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.263

Alfa AF: 0.192 Hom.: 586

Bravo AF: 0.267

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.60

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: rs935497; hg19: chr3-160600563;