19-45385658-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006663.4(PPP1R13L):​c.2152G>A​(p.Ala718Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,756 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: 6.8e-7 ( 0 hom. )

Consequence

PPP1R13L
NM_006663.4 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73
Variant links:
Genes affected
PPP1R13L (HGNC:18838): (protein phosphatase 1 regulatory subunit 13 like) IASPP is one of the most evolutionarily conserved inhibitors of p53 (TP53; MIM 191170), whereas ASPP1 (MIM 606455) and ASPP2 (MIM 602143) are activators of p53.[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R13LNM_006663.4 linkc.2152G>A p.Ala718Thr missense_variant Exon 11 of 13 ENST00000360957.10 NP_006654.2 Q8WUF5A0A024R0Q5
PPP1R13LNM_001142502.2 linkc.2152G>A p.Ala718Thr missense_variant Exon 11 of 13 NP_001135974.1 Q8WUF5A0A024R0Q5
PPP1R13LXM_017026177.2 linkc.2152G>A p.Ala718Thr missense_variant Exon 12 of 14 XP_016881666.1 Q8WUF5A0A024R0Q5
PPP1R13LXM_017026178.2 linkc.2152G>A p.Ala718Thr missense_variant Exon 12 of 14 XP_016881667.1 Q8WUF5A0A024R0Q5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R13LENST00000360957.10 linkc.2152G>A p.Ala718Thr missense_variant Exon 11 of 13 1 NM_006663.4 ENSP00000354218.4 Q8WUF5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460756
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726732
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:
8.99e-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

Inborn genetic diseases Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2152G>A (p.A718T) alteration is located in exon 11 (coding exon 10) of the PPP1R13L gene. This alteration results from a G to A substitution at nucleotide position 2152, causing the alanine (A) at amino acid position 718 to be replaced by a threonine (T). 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
0.87
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.0
L;L
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.021
D;D
Polyphen
1.0
D;D
Vest4
0.80
MutPred
0.42
Gain of glycosylation at A718 (P = 0.06);Gain of glycosylation at A718 (P = 0.06);
MVP
0.84
MPC
1.1
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.78
gMVP
0.60

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: rs888335796; hg19: chr19-45888916; API