11-74246161-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016147.3(PPME1):c.920A>G(p.Asn307Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,552,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PPME1
NM_016147.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

Publications

0 publications found

Variant links:

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 links:

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]

P4HA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07679215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPME1	NM_016147.3 link	c.920A>G	p.Asn307Ser	missense_variant	Exon 10 of 14	ENST00000328257.13	NP_057231.1	Q9Y570-1A0A140VK39
PPME1	NM_001271593.2 link	c.962A>G	p.Asn321Ser	missense_variant	Exon 10 of 14		NP_001258522.1	Q9Y570-4
PPME1	XM_047427116.1 link	c.920A>G	p.Asn307Ser	missense_variant	Exon 10 of 12		XP_047283072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13 link	c.920A>G	p.Asn307Ser	missense_variant	Exon 10 of 14	1	NM_016147.3	ENSP00000329867.8		Q9Y570-1
PPME1	ENST00000398427.6 link	c.962A>G	p.Asn321Ser	missense_variant	Exon 10 of 14	1		ENSP00000381461.4		Q9Y570-4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

160828

AF XY:

0.0000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1400726

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

690920

show subpopulations

African (AFR)

AF:

0.0000948

AC:

AN:

31662

American (AMR)

AF:

0.00

AC:

AN:

35762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

35828

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000176

AC:

AN:

1079462

Other (OTH)

AF:

0.0000515

AC:

AN:

58230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.920A>G (p.N307S) alteration is located in exon 10 (coding exon 10) of the PPME1 gene. This alteration results from a A to G substitution at nucleotide position 920, causing the asparagine (N) at amino acid position 307 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.093

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0077

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.22

N;.

PhyloP100

5.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.10

Sift

Benign

0.88

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

B;.

Vest4

0.11

MutPred

0.37

Loss of MoRF binding (P = 0.1224);.;

MVP

0.36

MPC

0.35

ClinPred

0.28

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.071

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-74246161-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over