Genetic Variant PPP1R13L:c.*180T>C (chr19-45380010-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006663.4(PPP1R13L):c.*180T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 677,488 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 74 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 21 hom. )

Consequence

PPP1R13L
NM_006663.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.681

Publications

1 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 -20 ACMG points.

BP4

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

BP6

Variant 19-45380010-A-G is Benign according to our data. Variant chr19-45380010-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0552 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.*180T>C		3_prime_UTR	Exon 13 of 13	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.*180T>C		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.*180T>C	3_prime_UTR	Exon 13 of 13	ENSP00000354218.4	Q8WUF5
PPP1R13L	ENST00000418234.6	TSL:1	c.*180T>C	3_prime_UTR	Exon 13 of 13	ENSP00000403902.1	Q8WUF5
PPP1R13L	ENST00000587270.5	TSL:1	n.2140T>C	non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2482

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0568

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.00208

AC:

1093

AN:

525254

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

483

AN XY:

277842

show subpopulations

African (AFR)

AF:

0.0575

AC:

802

AN:

13948

American (AMR)

AF:

0.00402

AC:

AN:

23626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13520

East Asian (EAS)

AF:

0.00

AC:

AN:

32318

South Asian (SAS)

AF:

0.000110

AC:

AN:

45540

European-Finnish (FIN)

AF:

0.0000300

AC:

AN:

33310

Middle Eastern (MID)

AF:

0.00227

AC:

AN:

2200

European-Non Finnish (NFE)

AF:

0.000120

AC:

AN:

332766

Other (OTH)

AF:

0.00517

AC:

145

AN:

28026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0164

AC:

2502

AN:

152234

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1186

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0571

AC:

2372

AN:

41522

American (AMR)

AF:

0.00556

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68022

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0123

Hom.:

Bravo

AF:

0.0184

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.2

(source)

DANN

Benign

0.79

PhyloP100

0.68

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