2-55573723-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001122964.3(PPP4R3B):​c.1661G>A​(p.Cys554Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PPP4R3B
NM_001122964.3 missense

Scores

10
3
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
PPP4R3B (HGNC:29267): (protein phosphatase 4 regulatory subunit 3B) Predicted to act upstream of or within positive regulation of gluconeogenesis and protein dephosphorylation. Located in centrosome and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPP4R3BNM_001122964.3 linkc.1661G>A p.Cys554Tyr missense_variant 12/17 ENST00000616407.2 NP_001116436.3 Q5MIZ7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPP4R3BENST00000616407.2 linkc.1661G>A p.Cys554Tyr missense_variant 12/171 NM_001122964.3 ENSP00000483228.1 Q5MIZ7-1
PPP4R3BENST00000616288.4 linkc.1565G>A p.Cys522Tyr missense_variant 11/161 ENSP00000484116.1 Q5MIZ7-2
PPP4R3BENST00000611717.4 linkc.1510+3592G>A intron_variant 1 ENSP00000478677.1 Q5MIZ7-3
PPP4R3BENST00000482826.1 linkn.-5G>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.19e-7
AC:
1
AN:
1390354
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
685252
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.29e-7
Gnomad4 OTH exome
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 15, 2021The c.1661G>A (p.C554Y) alteration is located in exon 12 (coding exon 12) of the PPP4R3B gene. This alteration results from a G to A substitution at nucleotide position 1661, causing the cysteine (C) at amino acid position 554 to be replaced by a tyrosine (Y). 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
1.0
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
.;T
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.079
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Uncertain
2.7
.;M
PrimateAI
Pathogenic
0.92
D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.82
MutPred
0.79
.;Gain of helix (P = 0.2059);
MVP
0.40
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.73
gMVP
0.74

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: rs1006605817; hg19: chr2-55800859; API