11-74187364-T-C

Variant names:

• chr11-74187364-T-C
• rs2848557
• NM_016147.3:c.101+15842T>C

Variant summary

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

The NM_016147.3(PPME1):​c.101+15842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,040 control chromosomes in the GnomAD database, including 36,141 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 0.69 (36141 hom., cov: 31)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016147.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPME1	NM_016147.3	MANE Select	c.101+15842T>C		intron	N/A	NP_057231.1	A0A140VK39
	PPME1	NM_001271593.2		c.101+15842T>C		intron	N/A	NP_001258522.1	Q9Y570-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPME1	ENST00000328257.13	TSL:1 MANE Select	c.101+15842T>C		intron	N/A	ENSP00000329867.8	Q9Y570-1
	PPME1	ENST00000398427.6	TSL:1	c.101+15842T>C		intron	N/A	ENSP00000381461.4	Q9Y570-4
	PPME1	ENST00000856423.1		c.101+15842T>C		intron	N/A	ENSP00000526482.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104425 AN: 151922 Hom.: 36099 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.687 AC: 104527 AN: 152040 Hom.: 36141 Cov.: 31 AF XY: 0.693 AC XY: 51519 AN XY: 74322

African (AFR) AF: 0.629 AC: 26075 AN: 41460

American (AMR) AF: 0.721 AC: 11018 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4373 AN: 5172

South Asian (SAS) AF: 0.765 AC: 3686 AN: 4820

European-Finnish (FIN) AF: 0.739 AC: 7807 AN: 10570

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.690 AC: 46901 AN: 67962

Other (OTH) AF: 0.687 AC: 1450 AN: 2110

Alfa AF: 0.685 Hom.: 5378

Bravo AF: 0.683

Asia WGS AF: 0.799 AC: 2776 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.93
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: rs2848557; hg19: chr11-73898409;