chr19-45385878-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_006663.4(PPP1R13L):āc.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
NM_006663.4 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 7.29
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]
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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 |
---|---|---|---|---|---|---|---|---|
PPP1R13L | NM_006663.4 | c.2027T>C | p.Val676Ala | missense_variant | 10/13 | ENST00000360957.10 | NP_006654.2 | |
PPP1R13L | NM_001142502.2 | c.2027T>C | p.Val676Ala | missense_variant | 10/13 | NP_001135974.1 | ||
PPP1R13L | XM_017026177.2 | c.2027T>C | p.Val676Ala | missense_variant | 11/14 | XP_016881666.1 | ||
PPP1R13L | XM_017026178.2 | c.2027T>C | p.Val676Ala | missense_variant | 11/14 | XP_016881667.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPP1R13L | ENST00000360957.10 | c.2027T>C | p.Val676Ala | missense_variant | 10/13 | 1 | NM_006663.4 | ENSP00000354218 | P1 | |
PPP1R13L | ENST00000418234.6 | c.2027T>C | p.Val676Ala | missense_variant | 10/13 | 1 | ENSP00000403902 | P1 | ||
PPP1R13L | ENST00000587270.5 | n.1500T>C | non_coding_transcript_exon_variant | 3/6 | 1 | |||||
PPP1R13L | ENST00000589858.1 | n.226T>C | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000335 AC: 81AN: 241796Hom.: 0 AF XY: 0.000464 AC XY: 61AN XY: 131436
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GnomAD4 exome AF: 0.000146 AC: 213AN: 1458786Hom.: 2 Cov.: 32 AF XY: 0.000189 AC XY: 137AN XY: 725510
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74340
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at