rs6966

Positions:

• chr19-45379704-T-A
• chr19-45379704-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006663.4(PPP1R13L):​c.*486A>T variant causes a 3 prime UTR 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 NM_006663.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13L	NM_006663.4	c.*486A>T		3_prime_UTR_variant	13/13	ENST00000360957.10
PPP1R13L	NM_001142502.2	c.*486A>T		3_prime_UTR_variant	13/13
PPP1R13L	XM_017026177.2	c.*486A>T		3_prime_UTR_variant	14/14
PPP1R13L	XM_017026178.2	c.*486A>T		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.*486A>T		3_prime_UTR_variant	13/13	1	NM_006663.4	P1

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

GnomAD3 exomes AF: 0.176 AC: 1037 AN: 5878 Hom.: 112 AF XY: 0.155 AC XY: 431 AN XY: 2772

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 SAS exome AF: 0.200

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

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.160

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

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.265

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs6966; hg19: chr19-45882962; COSMIC: COSV62908034; COSMIC: COSV62908034;