chr19-45385878-A-G

Position:

chr19-45385878-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_006663.4(PPP1R13L):c.2027T>C(p.Val676Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,610,964 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

PPP1R13L
NM_006663.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000789 (12/152178) while in subpopulation SAS AF= 0.00145 (7/4836). AF 95% confidence interval is 0.000679. There are 0 homozygotes in gnomad4. There are 10 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

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP1R13L	NM_006663.4 linkuse as main transcript	c.2027T>C	p.Val676Ala	missense_variant	10/13	ENST00000360957.10	NP_006654.2
PPP1R13L	NM_001142502.2 linkuse as main transcript	c.2027T>C	p.Val676Ala	missense_variant	10/13		NP_001135974.1
PPP1R13L	XM_017026177.2 linkuse as main transcript	c.2027T>C	p.Val676Ala	missense_variant	11/14		XP_016881666.1
PPP1R13L	XM_017026178.2 linkuse as main transcript	c.2027T>C	p.Val676Ala	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.2027T>C	p.Val676Ala	missense_variant	10/13	1	NM_006663.4	ENSP00000354218	P1
PPP1R13L	ENST00000418234.6 linkuse as main transcript	c.2027T>C	p.Val676Ala	missense_variant	10/13	1		ENSP00000403902	P1
PPP1R13L	ENST00000587270.5 linkuse as main transcript	n.1500T>C		non_coding_transcript_exon_variant	3/6	1
PPP1R13L	ENST00000589858.1 linkuse as main transcript	n.226T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000335

AC:

AN:

241796

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

131436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000773

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000734

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1458786

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

137

AN XY:

725510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000657

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000215

AC:

Asia WGS

AF:

0.000866

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

Oct 27, 2021

The c.2027T>C (p.V676A) alteration is located in exon 10 (coding exon 9) of the PPP1R13L gene. This alteration results from a T to C substitution at nucleotide position 2027, causing the valine (V) at amino acid position 676 to be replaced by an alanine (A). 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

0.82

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

.;T

M_CAP

Pathogenic

0.33

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;D

Vest4

0.78

MVP

0.86

MPC

1.1

ClinPred

0.10

GERP RS

4.7

Varity_R

0.91

gMVP

0.84

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