14-94237576-C-T

Variant summary

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

The NM_058237.2(PPP4R4):​c.743C>T​(p.Thr248Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T248R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PPP4R4
NM_058237.2 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.79
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 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
PPP4R4NM_058237.2 linkc.743C>T p.Thr248Ile missense_variant Exon 8 of 25 ENST00000304338.8 NP_478144.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP4R4ENST00000304338.8 linkc.743C>T p.Thr248Ile missense_variant Exon 8 of 25 1 NM_058237.2 ENSP00000305924.3 Q6NUP7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.57
D
MetaSVM
Uncertain
0.71
D
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-2.1
N
REVEL
Pathogenic
0.76
Sift
Benign
0.077
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.54
P
Vest4
0.64
MutPred
0.53
Gain of catalytic residue at L253 (P = 0);
MVP
0.62
MPC
0.64
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.25
gMVP
0.50

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: rs752895440; hg19: chr14-94703913; API