rs928911

Variant names:

• chr19-45404602-C-T
• rs928911
• NM_006663.4:c.-22+397G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006663.4(PPP1R13L):​c.-22+397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,246 control chromosomes in the GnomAD database, including 376 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 0.063 (376 hom., cov: 32)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.099 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.-22+397G>A		intron	N/A	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.-22+1690G>A		intron	N/A	NP_001135974.1	Q8WUF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.-22+397G>A		intron	N/A	ENSP00000354218.4	Q8WUF5
	PPP1R13L	ENST00000418234.6	TSL:1	c.-22+1690G>A		intron	N/A	ENSP00000403902.1	Q8WUF5
	PPP1R13L	ENST00000863739.1		c.-148+1690G>A		intron	N/A	ENSP00000533798.1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9522 AN: 152128 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0626 AC: 9529 AN: 152246 Hom.: 376 Cov.: 32 AF XY: 0.0638 AC XY: 4747 AN XY: 74438

African (AFR) AF: 0.102 AC: 4219 AN: 41538

American (AMR) AF: 0.0286 AC: 438 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.0411 AC: 213 AN: 5188

South Asian (SAS) AF: 0.0902 AC: 435 AN: 4820

European-Finnish (FIN) AF: 0.0844 AC: 895 AN: 10602

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2969 AN: 68016

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0478 Hom.: 336

Bravo AF: 0.0579

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		0.49
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs928911; hg19: chr19-45907860;