19-45400508-T-C

Variant names:

• chr19-45400508-T-C
• rs4572514
• NM_006663.4:c.-21-2169A>G

Variant summary

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

The NM_006663.4(PPP1R13L):​c.-21-2169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,810 control chromosomes in the GnomAD database, including 3,362 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 0.20 (3362 hom., cov: 30)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	NM_006663.4	MANE Select	c.-21-2169A>G		intron	N/A	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.-21-2169A>G		intron	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.-21-2169A>G		intron	N/A	ENSP00000354218.4	Q8WUF5
	PPP1R13L	ENST00000418234.6	TSL:1	c.-21-2169A>G		intron	N/A	ENSP00000403902.1	Q8WUF5
	PPP1R13L	ENST00000863739.1		c.-22+1491A>G		intron	N/A	ENSP00000533798.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30335 AN: 151700 Hom.: 3360 Cov.: 30

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.200 AC: 30347 AN: 151810 Hom.: 3362 Cov.: 30 AF XY: 0.205 AC XY: 15232 AN XY: 74154

African (AFR) AF: 0.209 AC: 8668 AN: 41498

American (AMR) AF: 0.226 AC: 3430 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3472

East Asian (EAS) AF: 0.444 AC: 2289 AN: 5160

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4826

European-Finnish (FIN) AF: 0.210 AC: 2177 AN: 10386

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11226 AN: 67972

Other (OTH) AF: 0.197 AC: 414 AN: 2104

Alfa AF: 0.183 Hom.: 4095

Bravo AF: 0.199

Asia WGS AF: 0.335 AC: 1163 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		1.7
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: rs4572514; hg19: chr19-45903766;