Genetic Variant PPP1R13L:p.Val828Gly (chr19-45380194-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006663.4(PPP1R13L):c.2483T>G(p.Val828Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V828A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PPP1R13L
NM_006663.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.77

Publications

0 publications found

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]

PPP1R13L Gene-Disease associations (from GenCC):

arrhythmogenic cardiomyopathy with variable ectodermal abnormalities
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
dilated cardiomyopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

PPP1R13L links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22602504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006663.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	NM_006663.4	MANE Select	c.2483T>G	p.Val828Gly	missense	Exon 13 of 13	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.2483T>G	p.Val828Gly	missense	Exon 13 of 13	NP_001135974.1	Q8WUF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.2483T>G	p.Val828Gly	missense	Exon 13 of 13	ENSP00000354218.4	Q8WUF5
PPP1R13L	ENST00000418234.6	TSL:1	c.2483T>G	p.Val828Gly	missense	Exon 13 of 13	ENSP00000403902.1	Q8WUF5
PPP1R13L	ENST00000587270.5	TSL:1	n.1956T>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.015

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.32

M_CAP

Benign

0.051

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.41

PhyloP100

2.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.86

Vest4

0.39

MutPred

0.25

Loss of stability (P = 0.0031)

MVP

0.62

MPC

0.83

ClinPred

0.57

GERP RS

4.6

Varity_R

0.34

gMVP

0.80

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over