chr14-103736034-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015316.3(PPP1R13B):​c.3200G>T​(p.Arg1067Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R1067Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PPP1R13B
NM_015316.3 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67
Variant links:
Genes affected
PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4071706).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R13BNM_015316.3 linkc.3200G>T p.Arg1067Leu missense_variant Exon 16 of 17 ENST00000202556.14 NP_056131.2 Q96KQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R13BENST00000202556.14 linkc.3200G>T p.Arg1067Leu missense_variant Exon 16 of 17 1 NM_015316.3 ENSP00000202556.9 Q96KQ4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249398
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135360
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461854
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727234
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.41
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.7
.;L
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.5
.;D
REVEL
Benign
0.21
Sift
Uncertain
0.0030
.;D
Sift4G
Uncertain
0.026
.;D
Polyphen
0.85
.;P
Vest4
0.62
MutPred
0.61
.;Gain of helix (P = 0.0143);
MVP
0.58
MPC
0.50
ClinPred
0.93
D
GERP RS
4.5
Varity_R
0.37
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs775532323; hg19: chr14-104202371; API