chr19-45382459-T-C

Position:

• chr19-45382459-T-C

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.2448+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,545,062 control chromosomes in the GnomAD database, including 132 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: 32)
  • Exomes 𝑓: 0.0017 (58 hom.)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0990

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=-0.85).
• BP6: Variant 19-45382459-T-C is Benign according to our data. Variant chr19-45382459-T-C is described in ClinVar as [Benign]. Clinvar id is 1249308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13L	NM_006663.4	c.2448+68A>G		intron_variant		ENST00000360957.10
PPP1R13L	NM_001142502.2	c.2448+68A>G		intron_variant
PPP1R13L	XM_017026177.2	c.2448+68A>G		intron_variant
PPP1R13L	XM_017026178.2	c.2448+68A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.2448+68A>G		intron_variant		1	NM_006663.4	P1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2466 AN: 152136 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

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: 0.0143

GnomAD4 exome AF: 0.00169 AC: 2353 AN: 1392808 Hom.: 58 AF XY: 0.00146 AC XY: 1002 AN XY: 687642

Gnomad4 AFR exome AF: 0.0564

Gnomad4 AMR exome AF: 0.00346

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.0000921

Gnomad4 OTH exome AF: 0.00496

GnomAD4 genome AF: 0.0163 AC: 2487 AN: 152254 Hom.: 74 Cov.: 32 AF XY: 0.0158 AC XY: 1177 AN XY: 74446

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0123 Hom.: 4

Bravo AF: 0.0184

Asia WGS AF: 0.00693 AC: 24 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 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.80

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: rs34383186; hg19: chr19-45885717;