Genetic Variant PPP1R13L:c.-22+1089T>C (chr19-45405203-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000418234.6(PPP1R13L):c.-22+1089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 206,644 control chromosomes in the GnomAD database, including 24,835 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 0.50 ( 20181 hom., cov: 31)

Exomes 𝑓: 0.41 ( 4654 hom. )

Consequence

PPP1R13L
ENST00000418234.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

35 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418234.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	NM_001142502.2		c.-22+1089T>C		intron	N/A	NP_001135974.1
	PPP1R13L	NM_006663.4	MANE Select	c.-226T>C		upstream_gene	N/A	NP_006654.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPP1R13L	ENST00000418234.6	TSL:1	c.-22+1089T>C	intron	N/A	ENSP00000403902.1
PPP1R13L	ENST00000593226.5	TSL:3	c.-104-122T>C	intron	N/A	ENSP00000466730.1
PPP1R13L	ENST00000585905.1	TSL:2	n.18+1089T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75583

AN:

151778

Hom.:

20147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.409

AC:

22417

AN:

54748

Hom.:

4654

AF XY:

0.408

AC XY:

10778

AN XY:

26418

show subpopulations

African (AFR)

AF:

0.642

AC:

614

AN:

956

American (AMR)

AF:

0.552

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

135

AN:

356

East Asian (EAS)

AF:

0.771

AC:

185

AN:

240

South Asian (SAS)

AF:

0.585

AC:

639

AN:

1092

European-Finnish (FIN)

AF:

0.376

AC:

160

AN:

426

Middle Eastern (MID)

AF:

0.418

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.398

AC:

19814

AN:

49794

Other (OTH)

AF:

0.462

AC:

787

AN:

1704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

678

1357

2035

2714

3392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.498

AC:

75674

AN:

151896

Hom.:

20181

Cov.:

AF XY:

0.502

AC XY:

37265

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.651

AC:

26955

AN:

41420

American (AMR)

AF:

0.577

AC:

8810

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1324

AN:

3466

East Asian (EAS)

AF:

0.755

AC:

3865

AN:

5116

South Asian (SAS)

AF:

0.579

AC:

2789

AN:

4818

European-Finnish (FIN)

AF:

0.372

AC:

3936

AN:

10572

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26411

AN:

67926

Other (OTH)

AF:

0.485

AC:

1022

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1819

3638

5457

7276

9095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.437

Hom.:

48105

Bravo

AF:

0.520

Asia WGS

AF:

0.665

AC:

2313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.8

(source)

DANN

Benign

0.59

PhyloP100

0.21

PromoterAI

0.10

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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