rs500608

Positions:

• chr11-74252696-C-A
• chr11-74252696-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016147.3(PPME1):​c.1143-796C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 340,902 control chromosomes in the GnomAD database, including 39,067 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 0.40 (14641 hom., cov: 31)
  • Exomes 𝑓: 0.50 (24426 hom.)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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]

P4HA3 (HGNC:30135): (prolyl 4-hydroxylase subunit alpha 3) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PPME1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPME1	NM_016147.3	c.1143-796C>A		intron_variant		ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.1185-796C>A		intron_variant			NP_001258522.1
P4HA3	XR_007062475.1	n.1946-2374G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.1143-796C>A		intron_variant		1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.1185-796C>A		intron_variant		1		ENSP00000381461.4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61343 AN: 151944 Hom.: 14626 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.498 AC: 93994 AN: 188840 Hom.: 24426 AF XY: 0.499 AC XY: 51678 AN XY: 103498

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.404 AC: 61375 AN: 152062 Hom.: 14641 Cov.: 31 AF XY: 0.405 AC XY: 30121 AN XY: 74334

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.463

Alfa AF: 0.497 Hom.: 16695

Bravo AF: 0.409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.54

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: rs500608; hg19: chr11-73963741;