chr19-45404702-A-G

Variant names:

• chr19-45404702-A-G
• rs4803817
• NM_006663.4:c.-22+297T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006663.4(PPP1R13L):​c.-22+297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,936 control chromosomes in the GnomAD database, including 6,440 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 0.28 (6440 hom., cov: 31)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 26 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
• dilated cardiomyopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	NM_006663.4	MANE Select	c.-22+297T>C		intron	N/A	NP_006654.2
	PPP1R13L	NM_001142502.2		c.-22+1590T>C		intron	N/A	NP_001135974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.-22+297T>C		intron	N/A	ENSP00000354218.4
	PPP1R13L	ENST00000418234.6	TSL:1	c.-22+1590T>C		intron	N/A	ENSP00000403902.1
	PPP1R13L	ENST00000593226.5	TSL:3	c.-22+297T>C		intron	N/A	ENSP00000466730.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42566 AN: 151816 Hom.: 6421 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.281 AC: 42634 AN: 151936 Hom.: 6440 Cov.: 31 AF XY: 0.280 AC XY: 20826 AN XY: 74292

African (AFR) AF: 0.373 AC: 15436 AN: 41380

American (AMR) AF: 0.354 AC: 5405 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1604 AN: 5160

South Asian (SAS) AF: 0.304 AC: 1462 AN: 4812

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10574

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15243 AN: 67962

Other (OTH) AF: 0.276 AC: 582 AN: 2112

Alfa AF: 0.246 Hom.: 9598

Bravo AF: 0.300

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		-0.16
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4803817; hg19: chr19-45907960;