chr19-45380190-CT-GA

Position:

• chr19-45380190-CT-GA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_006663.4(PPP1R13L):​c.2486_2487delinsTC​(p.Ter829PheextTer59) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPP1R13L NM_006663.4 stop_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.56

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_006663.4 Downstream stopcodon found after 12 codons.
• PP5: Variant 19-45380190-CT-GA is Pathogenic according to our data. Variant chr19-45380190-CT-GA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 974803.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13L	NM_006663.4	c.2486_2487delinsTC	p.Ter829PheextTer59	stop_lost	13/13	ENST00000360957.10
PPP1R13L	NM_001142502.2	c.2486_2487delinsTC	p.Ter829PheextTer59	stop_lost	13/13
PPP1R13L	XM_017026177.2	c.2486_2487delinsTC	p.Ter829PheextTer59	stop_lost	14/14
PPP1R13L	XM_017026178.2	c.2486_2487delinsTC	p.Ter829PheextTer59	stop_lost	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.2486_2487delinsTC	p.Ter829PheextTer59	stop_lost	13/13	1	NM_006663.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Primary dilated cardiomyopathy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Exeter Molecular Genetics Laboratory

Jun 10, 2020

This variant, NM_001142502.1:c.2486_2487delinsTC, was found in compound heterozygosity with the likely pathogenic variant NM_001142502.1:c.1610del. -

Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1972735240; hg19: chr19-45883448;