18-9550180-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042388.3(PPP4R1):​c.2419G>A​(p.Glu807Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PPP4R1
NM_001042388.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54
Variant links:
Genes affected
PPP4R1 (HGNC:9320): (protein phosphatase 4 regulatory subunit 1) This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP4R1NM_001042388.3 linkc.2419G>A p.Glu807Lys missense_variant Exon 18 of 20 ENST00000400556.8 NP_001035847.1 Q8TF05-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP4R1ENST00000400556.8 linkc.2419G>A p.Glu807Lys missense_variant Exon 18 of 20 1 NM_001042388.3 ENSP00000383402.3 Q8TF05-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249512
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135376
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 SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2419G>A (p.E807K) alteration is located in exon 18 (coding exon 18) of the PPP4R1 gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the glutamic acid (E) at amino acid position 807 to be replaced by a lysine (K). 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
Uncertain
0.43
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.28
Sift
Benign
0.31
T;T
Sift4G
Benign
0.52
T;T
Polyphen
0.57
P;B
Vest4
0.78
MVP
0.38
MPC
1.1
ClinPred
0.70
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs987030625; hg19: chr18-9550178; COSMIC: COSV99553531; COSMIC: COSV99553531; API