19-45379704-T-A

Variant names:

• chr19-45379704-T-A
• rs6966
• ENST00000587270.5:n.2446A>T

Variant summary

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

The ENST00000587270.5(PPP1R13L):​n.2446A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 156,236 control chromosomes in the GnomAD database, including 10,171 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 0.30 (10081 hom., cov: 31)
  • Exomes 𝑓: 0.17 (90 hom.)
• Consequence: PPP1R13L ENST00000587270.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 24 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587270.5. 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.*486A>T		3_prime_UTR	Exon 13 of 13	NP_006654.2
	PPP1R13L	NM_001142502.2		c.*486A>T		3_prime_UTR	Exon 13 of 13	NP_001135974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R13L	ENST00000587270.5	TSL:1	n.2446A>T		non_coding_transcript_exon	Exon 6 of 6
	PPP1R13L	ENST00000360957.10	TSL:1 MANE Select	c.*486A>T		3_prime_UTR	Exon 13 of 13	ENSP00000354218.4
	PPP1R13L	ENST00000418234.6	TSL:1	c.*486A>T		3_prime_UTR	Exon 13 of 13	ENSP00000403902.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46159 AN: 151940 Hom.: 10054 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.176 AC: 1037 AN: 5878 AF XY: 0.155

Gnomad AFR exome AF: 0.621

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.565

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.169 AC: 706 AN: 4178 Hom.: 90 Cov.: 0 AF XY: 0.173 AC XY: 375 AN XY: 2170

African (AFR) AF: 0.589 AC: 73 AN: 124

American (AMR) AF: 0.185 AC: 69 AN: 372

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 22 AN: 122

East Asian (EAS) AF: 0.452 AC: 85 AN: 188

South Asian (SAS) AF: 0.130 AC: 18 AN: 138

European-Finnish (FIN) AF: 0.130 AC: 41 AN: 316

Middle Eastern (MID) AF: 0.143 AC: 2 AN: 14

European-Non Finnish (NFE) AF: 0.134 AC: 357 AN: 2660

Other (OTH) AF: 0.160 AC: 39 AN: 244

GnomAD4 genome AF: 0.304 AC: 46236 AN: 152058 Hom.: 10081 Cov.: 31 AF XY: 0.303 AC XY: 22519 AN XY: 74328

African (AFR) AF: 0.608 AC: 25208 AN: 41448

American (AMR) AF: 0.267 AC: 4083 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2307 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1835 AN: 10576

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

European-Non Finnish (NFE) AF: 0.153 AC: 10436 AN: 67994

Other (OTH) AF: 0.265 AC: 561 AN: 2116

Alfa AF: 0.164 Hom.: 1542

Bravo AF: 0.330

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs6966; hg19: chr19-45882962; COSMIC: COSV62908034; COSMIC: COSV62908034;