19-45385658-C-T

Variant names:

• chr19-45385658-C-T
• rs888335796
• NM_006663.4:c.2152G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006663.4(PPP1R13L):​c.2152G>A​(p.Ala718Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPP1R13L NM_006663.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.2152G>A	p.Ala718Thr	missense_variant	Exon 11 of 13	ENST00000360957.10	NP_006654.2
PPP1R13L	NM_001142502.2	c.2152G>A	p.Ala718Thr	missense_variant	Exon 11 of 13		NP_001135974.1
PPP1R13L	XM_017026177.2	c.2152G>A	p.Ala718Thr	missense_variant	Exon 12 of 14		XP_016881666.1
PPP1R13L	XM_017026178.2	c.2152G>A	p.Ala718Thr	missense_variant	Exon 12 of 14		XP_016881667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.2152G>A	p.Ala718Thr	missense_variant	Exon 11 of 13	1	NM_006663.4	ENSP00000354218.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460756 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726732

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2152G>A (p.A718T) alteration is located in exon 11 (coding exon 10) of the PPP1R13L gene. This alteration results from a G to A substitution at nucleotide position 2152, causing the alanine (A) at amino acid position 718 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.42		Gain of glycosylation at A718 (P = 0.06);Gain of glycosylation at A718 (P = 0.06);
MVP		0.84
MPC		1.1
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.78
gMVP		0.60

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: rs888335796; hg19: chr19-45888916;