chr19-45380296-C-T

Variant names:

• chr19-45380296-C-T
• rs34004521
• NM_006663.4:c.2449-68G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006663.4(PPP1R13L):​c.2449-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,578,786 control chromosomes in the GnomAD database, including 17,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1229 hom., cov: 31)
  • Exomes 𝑓: 0.14 (16149 hom.)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.293
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-45380296-C-T is Benign according to our data. Variant chr19-45380296-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 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.2449-68G>A		intron	N/A	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.2449-68G>A		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.2449-68G>A		intron	N/A	ENSP00000354218.4	Q8WUF5
	PPP1R13L	ENST00000418234.6	TSL:1	c.2449-68G>A		intron	N/A	ENSP00000403902.1	Q8WUF5
	PPP1R13L	ENST00000587270.5	TSL:1	n.1922-68G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17076 AN: 151986 Hom.: 1230 Cov.: 31

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.145 AC: 206479 AN: 1426682 Hom.: 16149 AF XY: 0.146 AC XY: 104138 AN XY: 712126

African (AFR) AF: 0.0283 AC: 924 AN: 32700

American (AMR) AF: 0.0632 AC: 2823 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4577 AN: 25900

East Asian (EAS) AF: 0.0269 AC: 1063 AN: 39506

South Asian (SAS) AF: 0.156 AC: 13293 AN: 85412

European-Finnish (FIN) AF: 0.189 AC: 9997 AN: 52966

Middle Eastern (MID) AF: 0.159 AC: 781 AN: 4914

European-Non Finnish (NFE) AF: 0.153 AC: 164985 AN: 1081490

Other (OTH) AF: 0.136 AC: 8036 AN: 59160

GnomAD4 genome AF: 0.112 AC: 17074 AN: 152104 Hom.: 1229 Cov.: 31 AF XY: 0.113 AC XY: 8422 AN XY: 74356

African (AFR) AF: 0.0336 AC: 1394 AN: 41512

American (AMR) AF: 0.0854 AC: 1304 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3468

East Asian (EAS) AF: 0.0282 AC: 146 AN: 5176

South Asian (SAS) AF: 0.157 AC: 752 AN: 4798

European-Finnish (FIN) AF: 0.189 AC: 1998 AN: 10590

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10590 AN: 67968

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.136 Hom.: 2755

Bravo AF: 0.0979

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.65
PhyloP100		-0.29
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: rs34004521; hg19: chr19-45883554;