11-74172718-A-G

Variant names:

• chr11-74172718-A-G
• rs10501414
• NM_016147.3:c.101+1196A>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.101+1196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,150 control chromosomes in the GnomAD database, including 3,589 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 0.13 (3589 hom., cov: 32)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 1 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPME1	NM_016147.3	c.101+1196A>G		intron_variant	Intron 1 of 13	ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.101+1196A>G		intron_variant	Intron 1 of 13		NP_001258522.1
PPME1	XM_047427116.1	c.101+1196A>G		intron_variant	Intron 1 of 11		XP_047283072.1
PPME1	XM_017017913.3	c.101+1196A>G		intron_variant	Intron 1 of 9		XP_016873402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.101+1196A>G		intron_variant	Intron 1 of 13	1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.101+1196A>G		intron_variant	Intron 1 of 13	1		ENSP00000381461.4
PPME1	ENST00000542710.3	n.256+1196A>G		intron_variant	Intron 1 of 3	3
PPME1	ENST00000544401.2	n.180+1196A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19890 AN: 152032 Hom.: 3581 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.131 AC: 19948 AN: 152150 Hom.: 3589 Cov.: 32 AF XY: 0.127 AC XY: 9431 AN XY: 74416

African (AFR) AF: 0.413 AC: 17115 AN: 41414

American (AMR) AF: 0.0511 AC: 781 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5192

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4820

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0193 AC: 1311 AN: 68030

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0484 Hom.: 314

Bravo AF: 0.145

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10501414; hg19: chr11-73883763;