chr19-45385854-G-C

Position:

chr19-45385854-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_006663.4(PPP1R13L):c.2051C>G(p.Ala684Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,610,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

PPP1R13L
NM_006663.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30343717).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000263 (4/152232) while in subpopulation SAS AF= 0.000828 (4/4832). AF 95% confidence interval is 0.000282. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP1R13L	NM_006663.4 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	10/13	ENST00000360957.10	NP_006654.2
PPP1R13L	NM_001142502.2 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	10/13		NP_001135974.1
PPP1R13L	XM_017026177.2 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	11/14		XP_016881666.1
PPP1R13L	XM_017026178.2 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	11/14		XP_016881667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PPP1R13L	ENST00000360957.10 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	10/13	1	NM_006663.4	ENSP00000354218	P1
PPP1R13L	ENST00000418234.6 linkuse as main transcript	c.2051C>G	p.Ala684Gly	missense_variant	10/13	1		ENSP00000403902	P1
PPP1R13L	ENST00000587270.5 linkuse as main transcript	n.1524C>G		non_coding_transcript_exon_variant	3/6	1
PPP1R13L	ENST00000589858.1 linkuse as main transcript	n.250C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000456

AC:

AN:

241204

Hom.:

AF XY:

0.0000761

AC XY:

AN XY:

131330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000309

AC:

AN:

1458516

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

725466

show subpopulations

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:

0.000500

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000661

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.2051C>G (p.A684G) alteration is located in exon 10 (coding exon 9) of the PPP1R13L gene. This alteration results from a C to G substitution at nucleotide position 2051, causing the alanine (A) at amino acid position 684 to be replaced by a glycine (G). 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

0.77

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

.;D

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

0.28

B;B

Vest4

0.36

MVP

0.87

MPC

0.95

ClinPred

0.46

GERP RS

3.8

Varity_R

0.94

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over