dbSNP rs6966: PPP1R13L:n.2446A>T (chr19-45379704-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000587270.5(PPP1R13L):n.2446A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 156,236 control chromosomes in the GnomAD database, including 10,171 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 10081 hom., cov: 31)

Exomes 𝑓: 0.17 ( 90 hom. )

Consequence

PPP1R13L
ENST00000587270.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.256

Publications

24 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
dilated cardiomyopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

PPP1R13L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PPP1R13L	NM_006663.4 link	c.*486A>T	3_prime_UTR_variant	Exon 13 of 13	ENST00000360957.10	NP_006654.2
PPP1R13L	NM_001142502.2 link	c.*486A>T	3_prime_UTR_variant	Exon 13 of 13		NP_001135974.1
PPP1R13L	XM_017026177.2 link	c.*486A>T	3_prime_UTR_variant	Exon 14 of 14		XP_016881666.1
PPP1R13L	XM_017026178.2 link	c.*486A>T	3_prime_UTR_variant	Exon 14 of 14		XP_016881667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10 link	c.*486A>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_006663.4	ENSP00000354218.4

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46159

AN:

151940

Hom.:

10054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.176

AC:

1037

AN:

5878

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.169

AC:

706

AN:

4178

Hom.:

Cov.:

AF XY:

0.173

AC XY:

375

AN XY:

2170

show subpopulations

African (AFR)

AF:

0.589

AC:

AN:

124

American (AMR)

AF:

0.185

AC:

AN:

372

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

AN:

122

East Asian (EAS)

AF:

0.452

AC:

AN:

188

South Asian (SAS)

AF:

0.130

AC:

AN:

138

European-Finnish (FIN)

AF:

0.130

AC:

AN:

316

Middle Eastern (MID)

AF:

0.143

AC:

AN:

European-Non Finnish (NFE)

AF:

0.134

AC:

357

AN:

2660

Other (OTH)

AF:

0.160

AC:

AN:

244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.304

AC:

46236

AN:

152058

Hom.:

10081

Cov.:

AF XY:

0.303

AC XY:

22519

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.608

AC:

25208

AN:

41448

American (AMR)

AF:

0.267

AC:

4083

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

657

AN:

3468

East Asian (EAS)

AF:

0.447

AC:

2307

AN:

5164

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4820

European-Finnish (FIN)

AF:

0.174

AC:

1835

AN:

10576

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10436

AN:

67994

Other (OTH)

AF:

0.265

AC:

561

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1361

2721

4082

5442

6803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

1542

Bravo

AF:

0.330

Asia WGS

AF:

0.369

AC:

1282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.7

(source)

DANN

Benign

0.70

PhyloP100

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over