ENST00000418234.6:c.-22+500G>A

Variant names:

• chr19-45405792-C-T
• rs1005165
• ENST00000418234.6:c.-22+500G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000418234.6(PPP1R13L):​c.-22+500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,120 control chromosomes in the GnomAD database, including 3,949 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 0.22 (3949 hom., cov: 32)
• Consequence: PPP1R13L ENST00000418234.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 25 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R13L	NM_001142502.2	c.-22+500G>A		intron_variant	Intron 1 of 12		NP_001135974.1
PPP1R13L	XM_017026177.2	c.-105+500G>A		intron_variant	Intron 1 of 13		XP_016881666.1
PPP1R13L	XM_017026178.2	c.-148+500G>A		intron_variant	Intron 1 of 13		XP_016881667.1
PPP1R13L	XM_017026179.2	c.-22+500G>A		intron_variant	Intron 1 of 8		XP_016881668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000418234.6	c.-22+500G>A		intron_variant	Intron 1 of 12	1		ENSP00000403902.1
PPP1R13L	ENST00000593226.5	c.-105+500G>A		intron_variant	Intron 1 of 4	3		ENSP00000466730.1
PPP1R13L	ENST00000585905.1	n.18+500G>A		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33066 AN: 152002 Hom.: 3945 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.218 AC: 33098 AN: 152120 Hom.: 3949 Cov.: 32 AF XY: 0.222 AC XY: 16476 AN XY: 74370

African (AFR) AF: 0.278 AC: 11553 AN: 41506

American (AMR) AF: 0.223 AC: 3408 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2292 AN: 5156

South Asian (SAS) AF: 0.276 AC: 1329 AN: 4818

European-Finnish (FIN) AF: 0.200 AC: 2115 AN: 10598

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.164 AC: 11153 AN: 67968

Other (OTH) AF: 0.209 AC: 441 AN: 2110

Alfa AF: 0.174 Hom.: 2405

Bravo AF: 0.220

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.96
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1005165; hg19: chr19-45909050;