14-94242373-C-T

Variant summary

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

The NM_058237.2(PPP4R4):​c.1231C>T​(p.Pro411Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P411A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PPP4R4
NM_058237.2 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94
Variant links:
Genes affected
PPP4R4 (HGNC:23788): (protein phosphatase 4 regulatory subunit 4) The protein encoded by this gene is a HEAT-like repeat-containing protein. The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins. Arrays of HEAT repeats form a rod-like helical structure and appear to function as protein-protein interaction surfaces. The repeat-containing region of this protein has some similarity to the constant regulatory domain of the protein phosphatase 2A PR65/A subunit. The encoded protein binds protein serine/threonine phosphatase 4c in the cytoplasm. [provided by RefSeq, Jan 2017]

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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=0.15811926).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP4R4NM_058237.2 linkc.1231C>T p.Pro411Ser missense_variant Exon 11 of 25 ENST00000304338.8 NP_478144.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP4R4ENST00000304338.8 linkc.1231C>T p.Pro411Ser missense_variant Exon 11 of 25 1 NM_058237.2 ENSP00000305924.3 Q6NUP7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458334
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725790
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
20
DANN
Benign
0.23
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.17
Eigen_PC
Benign
0.047
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.16
T
MetaSVM
Uncertain
-0.0040
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.22
Sift
Benign
0.80
T
Sift4G
Benign
0.32
T
Polyphen
0.028
B
Vest4
0.20
MutPred
0.43
Gain of catalytic residue at D407 (P = 0.001);
MVP
0.60
MPC
0.29
ClinPred
0.49
T
GERP RS
5.3
Varity_R
0.098
gMVP
0.15

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: chr14-94708710; API