11-74206145-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PPME1	NM_016147.3	c.288+1700A>G		intron_variant		ENST00000328257.13
PPME1	NM_001271593.2	c.288+1700A>G		intron_variant
PPME1	XM_017017913.3	c.288+1700A>G		intron_variant
PPME1	XM_047427116.1	c.288+1700A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPME1	ENST00000328257.13	c.288+1700A>G		intron_variant		1	NM_016147.3	P1
PPME1	ENST00000398427.6	c.288+1700A>G		intron_variant		1
PPME1	ENST00000544401.2	n.367+1700A>G		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.879

Alfa AF: 0.811 Hom.: 22303

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

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: rs544356; hg19: chr11-73917190;