rs10513560

Positions:

• chr3-160993010-G-A

Variant summary

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

The ENST00000498165.6(PPM1L):​c.574+31100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,756 control chromosomes in the GnomAD database, including 18,192 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 0.47 (18192 hom., cov: 31)
• Consequence: PPM1L ENST00000498165.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1L	NM_139245.4	c.574+31100G>A		intron_variant		ENST00000498165.6	NP_640338.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1L	ENST00000498165.6	c.574+31100G>A		intron_variant		1	NM_139245.4	ENSP00000417659	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71493 AN: 151638 Hom.: 18146 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.472 AC: 71604 AN: 151756 Hom.: 18192 Cov.: 31 AF XY: 0.473 AC XY: 35049 AN XY: 74132

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.460

Alfa AF: 0.404 Hom.: 6746

Bravo AF: 0.493

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.68

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: rs10513560; hg19: chr3-160710798; COSMIC: COSV99862392;