rs928911

chr19-45404602-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13L	NM_006663.4	c.-22+397G>A		intron_variant		ENST00000360957.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.-22+397G>A		intron_variant		1	NM_006663.4	P1

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.0411

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.0844

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0530 Hom.: 94

Bravo AF: 0.0579

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.6
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs928911; hg19: chr19-45907860;