rs10898966

Variant names:

• chr11-74249059-C-T
• rs10898966
• NM_016147.3:c.1010-1895C>T

Variant summary

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

The NM_016147.3(PPME1):​c.1010-1895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,214 control chromosomes in the GnomAD database, including 2,591 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 0.18 (2591 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• 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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPME1	NM_016147.3	c.1010-1895C>T		intron_variant	Intron 11 of 13	ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.1052-1895C>T		intron_variant	Intron 11 of 13		NP_001258522.1
PPME1	XM_047427116.1	c.1010-1895C>T		intron_variant	Intron 11 of 11		XP_047283072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.1010-1895C>T		intron_variant	Intron 11 of 13	1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.1052-1895C>T		intron_variant	Intron 11 of 13	1		ENSP00000381461.4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26926 AN: 152092 Hom.: 2592 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.177 AC: 26935 AN: 152210 Hom.: 2591 Cov.: 32 AF XY: 0.184 AC XY: 13682 AN XY: 74414

African (AFR) AF: 0.171 AC: 7103 AN: 41530

American (AMR) AF: 0.109 AC: 1671 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1541 AN: 5178

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3423 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11171 AN: 67994

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.166 Hom.: 540

Bravo AF: 0.157

Asia WGS AF: 0.245 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.82
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10898966; hg19: chr11-73960104;