Genetic Variant PPME1:c.1143-796C>T (chr11-74252696-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016147.3(PPME1):c.1143-796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 341,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

PPME1
NM_016147.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Publications

7 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:

ENSG00000206913 (HGNC:):

ENSG00000206913 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPME1	NM_016147.3 link	c.1143-796C>T	intron_variant	Intron 13 of 13	ENST00000328257.13	NP_057231.1	Q9Y570-1A0A140VK39
PPME1	NM_001271593.2 link	c.1185-796C>T	intron_variant	Intron 13 of 13		NP_001258522.1	Q9Y570-4
P4HA3	XR_007062475.1 link	n.1946-2374G>A	intron_variant	Intron 14 of 14
LOC124902824	XR_007063005.1 link	n.-144G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13 link	c.1143-796C>T		intron_variant	Intron 13 of 13	1	NM_016147.3	ENSP00000329867.8		Q9Y570-1
PPME1	ENST00000398427.6 link	c.1185-796C>T		intron_variant	Intron 13 of 13	1		ENSP00000381461.4		Q9Y570-4

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000294

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000206

AC:

AN:

189388

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

103812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5368

American (AMR)

AF:

0.000702

AC:

AN:

12824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4310

East Asian (EAS)

AF:

0.00

AC:

AN:

8092

South Asian (SAS)

AF:

0.00

AC:

AN:

39452

European-Finnish (FIN)

AF:

0.000125

AC:

AN:

7986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

640

European-Non Finnish (NFE)

AF:

0.000275

AC:

AN:

101658

Other (OTH)

AF:

0.000110

AC:

AN:

9058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000164

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41516

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

67988

Other (OTH)

AF:

0.000474

AC:

AN:

2110

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

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

21906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.062

(source)

DANN

Benign

0.48

PhyloP100

-2.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over