dbSNP rs6966: PPP1R13L:c.*486A>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 NM_006663.4(PPP1R13L):c.*486A>T variant causes a 3 prime UTR 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
NM_006663.4 3_prime_UTR

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, ClinGen
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.

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.*486A>T		3_prime_UTR	Exon 13 of 13	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.*486A>T		3_prime_UTR	Exon 13 of 13	NP_001135974.1	Q8WUF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.*486A>T	3_prime_UTR	Exon 13 of 13	ENSP00000354218.4	Q8WUF5
PPP1R13L	ENST00000418234.6	TSL:1	c.*486A>T	3_prime_UTR	Exon 13 of 13	ENSP00000403902.1	Q8WUF5
PPP1R13L	ENST00000587270.5	TSL:1	n.2446A>T	non_coding_transcript_exon	Exon 6 of 6

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over