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):ā€‹c.2027T>Cā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.00015 ( 2 hom. )

Consequence

PPP1R13L
NM_006663.4 missense

Scores

3
10
6

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]

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 UniProt
PPP1R13LNM_006663.4 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 10/13 ENST00000360957.10 NP_006654.2
PPP1R13LNM_001142502.2 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 10/13 NP_001135974.1
PPP1R13LXM_017026177.2 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 11/14 XP_016881666.1
PPP1R13LXM_017026178.2 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 11/14 XP_016881667.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPP1R13LENST00000360957.10 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 10/131 NM_006663.4 ENSP00000354218 P1
PPP1R13LENST00000418234.6 linkuse as main transcriptc.2027T>C p.Val676Ala missense_variant 10/131 ENSP00000403902 P1
PPP1R13LENST00000587270.5 linkuse as main transcriptn.1500T>C non_coding_transcript_exon_variant 3/61
PPP1R13LENST00000589858.1 linkuse as main transcriptn.226T>C non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152178
Hom.:
0
Cov.:
32
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:
81
AN:
241796
Hom.:
0
AF XY:
0.000464
AC XY:
61
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.:
2
Cov.:
32
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:
12
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
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.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.000215
AC:
26
Asia WGS
AF:
0.000866
AC:
3
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 submitterclinical testingAmbry GeneticsOct 27, 2021The 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
T
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.67
.;T
M_CAP
Pathogenic
0.33
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.5
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
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
T
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.

Other links and lift over

dbSNP: rs773587395; hg19: chr19-45889136; API