19-45405203-A-G

Position:

• chr19-45405203-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142502.2(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 NM_001142502.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R13L	NM_001142502.2	c.-22+1089T>C		intron_variant			NP_001135974.1
PPP1R13L	XM_017026177.2	c.-104-122T>C		intron_variant			XP_016881666.1
PPP1R13L	XM_017026178.2	c.-148+1089T>C		intron_variant			XP_016881667.1
PPP1R13L	XM_017026179.2	c.-22+1089T>C		intron_variant			XP_016881668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000418234.6	c.-22+1089T>C		intron_variant		1		ENSP00000403902.1
PPP1R13L	ENST00000593226.5	c.-104-122T>C		intron_variant		3		ENSP00000466730.1
PPP1R13L	ENST00000585905.1	n.18+1089T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75583 AN: 151778 Hom.: 20147 Cov.: 31

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

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.498 AC: 75674 AN: 151896 Hom.: 20181 Cov.: 31 AF XY: 0.502 AC XY: 37265 AN XY: 74254

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.485

Alfa AF: 0.423 Hom.: 15987

Bravo AF: 0.520

Asia WGS AF: 0.665 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10412761; hg19: chr19-45908461; COSMIC: COSV56237129; COSMIC: COSV56237129;