8-9141363-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024607.4(PPP1R3B):​c.289G>C​(p.Asp97His) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,094 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PPP1R3B
NM_024607.4 missense

Scores

9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23
Variant links:
Genes affected
PPP1R3B (HGNC:14942): (protein phosphatase 1 regulatory subunit 3B) This gene encodes the catalytic subunit of the serine/theonine phosphatase, protein phosphatase-1. The encoded protein is expressed in liver and skeletal muscle tissue and may be involved in regulating glycogen synthesis in these tissues. This gene may be a involved in type 2 diabetes and maturity-onset diabetes of the young. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34305048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R3BNM_024607.4 linkc.289G>C p.Asp97His missense_variant Exon 2 of 2 ENST00000310455.4 NP_078883.2 Q86XI6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R3BENST00000310455.4 linkc.289G>C p.Asp97His missense_variant Exon 2 of 2 1 NM_024607.4 ENSP00000308318.3 Q86XI6

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000955
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461882
Hom.:
0
Cov.:
35
AF XY:
0.00000825
AC XY:
6
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289G>C (p.D97H) alteration is located in exon 2 (coding exon 1) of the PPP1R3B gene. This alteration results from a G to C substitution at nucleotide position 289, causing the aspartic acid (D) at amino acid position 97 to be replaced by a histidine (H). 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
Benign
0.19
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Benign
0.10
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.014
D;D
Polyphen
0.96
D;D
Vest4
0.30
MutPred
0.36
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
0.74
MPC
0.16
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.37
gMVP
0.63

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: rs950903378; hg19: chr8-8998873; API