11-74206145-A-G

Variant names:

• chr11-74206145-A-G
• rs544356
• NM_016147.3:c.288+1700A>G

Variant summary

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

The NM_016147.3(PPME1):​c.288+1700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,200 control chromosomes in the GnomAD database, including 56,256 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 0.86 (56256 hom., cov: 32)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 4 publications found

Genes affected

PPME1 (HGNC:30178): (protein phosphatase methylesterase 1) This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPME1	NM_016147.3	c.288+1700A>G		intron_variant	Intron 3 of 13	ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.288+1700A>G		intron_variant	Intron 3 of 13		NP_001258522.1
PPME1	XM_047427116.1	c.288+1700A>G		intron_variant	Intron 3 of 11		XP_047283072.1
PPME1	XM_017017913.3	c.288+1700A>G		intron_variant	Intron 3 of 9		XP_016873402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.288+1700A>G		intron_variant	Intron 3 of 13	1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.288+1700A>G		intron_variant	Intron 3 of 13	1		ENSP00000381461.4
PPME1	ENST00000544401.2	n.367+1700A>G		intron_variant	Intron 3 of 4	4
PPME1	ENST00000542710.3	n.*222A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130300 AN: 152082 Hom.: 56181 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.857 AC: 130435 AN: 152200 Hom.: 56256 Cov.: 32 AF XY: 0.860 AC XY: 63980 AN XY: 74422

African (AFR) AF: 0.957 AC: 39745 AN: 41544

American (AMR) AF: 0.850 AC: 12981 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3035 AN: 3470

East Asian (EAS) AF: 0.869 AC: 4509 AN: 5186

South Asian (SAS) AF: 0.916 AC: 4426 AN: 4830

European-Finnish (FIN) AF: 0.817 AC: 8648 AN: 10582

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54226 AN: 67992

Other (OTH) AF: 0.879 AC: 1858 AN: 2114

Alfa AF: 0.821 Hom.: 40009

Bravo AF: 0.864

Asia WGS AF: 0.908 AC: 3158 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		-0.61
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: rs544356; hg19: chr11-73917190;