19-45380296-C-T

Position:

• chr19-45380296-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006663.4(PPP1R13L):​c.2449-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,578,786 control chromosomes in the GnomAD database, including 17,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1229 hom., cov: 31)
  • Exomes 𝑓: 0.14 (16149 hom.)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.293

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-45380296-C-T is Benign according to our data. Variant chr19-45380296-C-T is described in ClinVar as [Benign]. Clinvar id is 1234747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.2449-68G>A		intron_variant		ENST00000360957.10	NP_006654.2
PPP1R13L	NM_001142502.2	c.2449-68G>A		intron_variant			NP_001135974.1
PPP1R13L	XM_017026177.2	c.2449-68G>A		intron_variant			XP_016881666.1
PPP1R13L	XM_017026178.2	c.2449-68G>A		intron_variant			XP_016881667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.2449-68G>A		intron_variant		1	NM_006663.4	ENSP00000354218	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17076 AN: 151986 Hom.: 1230 Cov.: 31

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.145 AC: 206479 AN: 1426682 Hom.: 16149 AF XY: 0.146 AC XY: 104138 AN XY: 712126

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.0632

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.112 AC: 17074 AN: 152104 Hom.: 1229 Cov.: 31 AF XY: 0.113 AC XY: 8422 AN XY: 74356

Gnomad4 AFR AF: 0.0336

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.111

Alfa AF: 0.144 Hom.: 394

Bravo AF: 0.0979

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.65

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: rs34004521; hg19: chr19-45883554;