chr19-813642-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001270366.2(PLPPR3):​c.1085G>A​(p.Arg362His) variant causes a missense change. The variant allele was found at a frequency of 0.0000065 in 1,538,916 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

PLPPR3
NM_001270366.2 missense

Scores

2
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58
Variant links:
Genes affected
PLPPR3 (HGNC:23497): (phospholipid phosphatase related 3) The proteins in the lipid phosphate phosphatase (LPP) family, including PRG2, are integral membrane proteins that modulate bioactive lipid phosphates including phosphatidate, lysophosphatidate, and sphingosine-1-phosphate in the context of cell migration, neurite retraction, and mitogenesis (Brauer et al., 2003 [PubMed 12730698]).[supplied by OMIM, Mar 2008]
MIR3187 (HGNC:38319): (microRNA 3187) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34580475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLPPR3NM_001270366.2 linkc.1085G>A p.Arg362His missense_variant Exon 8 of 8 ENST00000520876.8 NP_001257295.1 Q6T4P5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLPPR3ENST00000520876.8 linkc.1085G>A p.Arg362His missense_variant Exon 8 of 8 1 NM_001270366.2 ENSP00000430297.1 Q6T4P5-1
PLPPR3ENST00000359894.6 linkc.1169G>A p.Arg390His missense_variant Exon 7 of 7 1 ENSP00000352962.2 Q6T4P5-3
MIR3187ENST00000583431.1 linkn.59C>T non_coding_transcript_exon_variant Exon 1 of 1 6
PLPPR3ENST00000517665.2 linkc.*114G>A downstream_gene_variant 3 ENSP00000430544.3 H0YBY4

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000757
AC:
1
AN:
132038
Hom.:
0
AF XY:
0.0000139
AC XY:
1
AN XY:
71744
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000208
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000649
AC:
9
AN:
1386890
Hom.:
0
Cov.:
35
AF XY:
0.00000730
AC XY:
5
AN XY:
684474
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:
0.00
Gnomad4 FIN exome
AF:
0.0000249
Gnomad4 NFE exome
AF:
0.00000650
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152026
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000441
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1169G>A (p.R390H) alteration is located in exon 7 (coding exon 6) of the PLPPR3 gene. This alteration results from a G to A substitution at nucleotide position 1169, causing the arginine (R) at amino acid position 390 to be replaced by a histidine (H). 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
Benign
0.19
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
.;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-0.85
T
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.18
Sift
Benign
0.037
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;P
Vest4
0.75
MutPred
0.41
.;Loss of ubiquitination at K367 (P = 0.0367);
MVP
0.45
MPC
1.3
ClinPred
0.98
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.41

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: rs1397804140; hg19: chr19-813642; API