18-9557301-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042388.3(PPP4R1):​c.2110G>C​(p.Val704Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000098 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

PPP4R1
NM_001042388.3 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19396529).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP4R1NM_001042388.3 linkc.2110G>C p.Val704Leu missense_variant Exon 15 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.2110G>C p.Val704Leu missense_variant Exon 15 of 20 1 NM_001042388.3 ENSP00000383402.3 Q8TF05-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000169
AC:
42
AN:
248520
Hom.:
0
AF XY:
0.000178
AC XY:
24
AN XY:
134866
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000585
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000142
Gnomad OTH exome
AF:
0.000332
GnomAD4 exome
AF:
0.0000972
AC:
142
AN:
1460754
Hom.:
0
Cov.:
30
AF XY:
0.000103
AC XY:
75
AN XY:
726696
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000607
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000814
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000837
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000265
AC:
32
EpiCase
AF:
0.000437
EpiControl
AF:
0.000415

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2110G>C (p.V704L) alteration is located in exon 15 (coding exon 15) of the PPP4R1 gene. This alteration results from a G to C substitution at nucleotide position 2110, causing the valine (V) at amino acid position 704 to be replaced by a leucine (L). 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
Pathogenic
0.59
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.038
T;.
Eigen
Benign
0.017
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.98
L;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.14
Sift
Benign
0.057
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.076
B;B
Vest4
0.86
MVP
0.093
MPC
0.76
ClinPred
0.034
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.18
gMVP
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs184708932; hg19: chr18-9557299; API