19-45400508-T-C

Position:

• chr19-45400508-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.-21-2169A>G		intron_variant		ENST00000360957.10	NP_006654.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.-21-2169A>G		intron_variant		1	NM_006663.4	ENSP00000354218	P1

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

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.197

Alfa AF: 0.181 Hom.: 391

Bravo AF: 0.199

Asia WGS AF: 0.335 AC: 1163 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.78

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: rs4572514; hg19: chr19-45903766;