19-45380010-A-C

Variant names:

• chr19-45380010-A-C
• rs112443418
• NM_006663.4:c.*180T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006663.4(PPP1R13L):​c.*180T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 525,262 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: PPP1R13L NM_006663.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.*180T>G		3_prime_UTR	Exon 13 of 13	NP_006654.2	Q8WUF5
	PPP1R13L	NM_001142502.2		c.*180T>G		3_prime_UTR	Exon 13 of 13	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.*180T>G		3_prime_UTR	Exon 13 of 13	ENSP00000354218.4	Q8WUF5
	PPP1R13L	ENST00000418234.6	TSL:1	c.*180T>G		3_prime_UTR	Exon 13 of 13	ENSP00000403902.1	Q8WUF5
	PPP1R13L	ENST00000587270.5	TSL:1	n.2140T>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000190 AC: 1 AN: 525262 Hom.: 0 Cov.: 7 AF XY: 0.00000360 AC XY: 1 AN XY: 277846

African (AFR) AF: 0.00 AC: 0 AN: 13952

American (AMR) AF: 0.00 AC: 0 AN: 23628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13520

East Asian (EAS) AF: 0.00 AC: 0 AN: 32318

South Asian (SAS) AF: 0.00 AC: 0 AN: 45540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2200

European-Non Finnish (NFE) AF: 0.00000301 AC: 1 AN: 332766

Other (OTH) AF: 0.00 AC: 0 AN: 28028

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112443418; hg19: chr19-45883268;