chr19-45380190-CT-GA

Variant names:

• chr19-45380190-CT-GA
• rs1972735240
• NM_006663.4:c.2486_2487delAGinsTC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP5_Moderate

The NM_006663.4(PPP1R13L):​c.2486_2487delAGinsTC​(p.Ter829Pheext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• arrhythmogenic cardiomyopathy with variable ectodermal abnormalities

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• dilated cardiomyopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM4: Stoplost variant in NM_006663.4 Downstream stopcodon found after 45 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 VariationId is 974803.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006663.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	NM_006663.4	MANE Select	c.2486_2487delAGinsTC	p.Ter829Pheext*?	stop_lost	N/A	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.2486_2487delAGinsTC	p.Ter829Pheext*?	stop_lost	N/A	NP_001135974.1	Q8WUF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.2486_2487delAGinsTC	p.Ter829Pheext*?	stop_lost	N/A	ENSP00000354218.4	Q8WUF5
	PPP1R13L	ENST00000418234.6	TSL:1	c.2486_2487delAGinsTC	p.Ter829Pheext*?	stop_lost	N/A	ENSP00000403902.1	Q8WUF5
	PPP1R13L	ENST00000587270.5	TSL:1	n.1959_1960delAGinsTC		non_coding_transcript_exon	Exon 6 of 6

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

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities (1)
1	-	-	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

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

Other links and lift over

dbSNP: rs1972735240; hg19: chr19-45883448;