11-74187364-T-C

Position:

• chr11-74187364-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

PPME1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPME1	NM_016147.3	c.101+15842T>C		intron_variant		ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.101+15842T>C		intron_variant			NP_001258522.1
PPME1	XM_047427116.1	c.101+15842T>C		intron_variant			XP_047283072.1
PPME1	XM_017017913.3	c.101+15842T>C		intron_variant			XP_016873402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.101+15842T>C		intron_variant		1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.101+15842T>C		intron_variant		1		ENSP00000381461.4
PPME1	ENST00000542710.3	n.256+15842T>C		intron_variant		3
PPME1	ENST00000544401.2	n.180+15842T>C		intron_variant		4

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

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.687

Alfa AF: 0.687 Hom.: 5225

Bravo AF: 0.683

Asia WGS AF: 0.799 AC: 2776 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.69

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: rs2848557; hg19: chr11-73898409;