18-9549256-C-A

Variant summary

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

The NM_001042388.3(PPP4R1):​c.2630G>T​(p.Arg877Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R877G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PPP4R1
NM_001042388.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03
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.2630G>T p.Arg877Met missense_variant Exon 19 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.2630G>T p.Arg877Met missense_variant Exon 19 of 20 1 NM_001042388.3 ENSP00000383402.3 Q8TF05-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2630G>T (p.R877M) alteration is located in exon 19 (coding exon 19) of the PPP4R1 gene. This alteration results from a G to T substitution at nucleotide position 2630, causing the arginine (R) at amino acid position 877 to be replaced by a methionine (M). 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
0.40
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.11
Sift
Benign
0.041
D;D
Sift4G
Uncertain
0.043
D;D
Polyphen
0.90
P;P
Vest4
0.55
MutPred
0.38
Loss of solvent accessibility (P = 0.1115);.;
MVP
0.15
MPC
1.8
ClinPred
0.80
D
GERP RS
5.7
Varity_R
0.11
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-9549254; API