19-45385923-A-G

Variant names:

• chr19-45385923-A-G
• NM_006663.4:c.1982T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006663.4(PPP1R13L):​c.1982T>C​(p.Ile661Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPP1R13L NM_006663.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.1982T>C	p.Ile661Thr	missense_variant	Exon 10 of 13	ENST00000360957.10	NP_006654.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.1982T>C	p.Ile661Thr	missense_variant	Exon 10 of 13	1	NM_006663.4	ENSP00000354218.4
PPP1R13L	ENST00000418234.6	c.1982T>C	p.Ile661Thr	missense_variant	Exon 10 of 13	1		ENSP00000403902.1
PPP1R13L	ENST00000587270.5	n.1455T>C		non_coding_transcript_exon_variant	Exon 3 of 6	1
PPP1R13L	ENST00000589858.1	n.181T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460330 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726408

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		1.0	D;D
Vest4		0.86
MutPred		0.50		Gain of glycosylation at I661 (P = 0.0046);Gain of glycosylation at I661 (P = 0.0046);
MVP		0.89
MPC		0.94
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45889181;