chr3-142669455-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001145319.2(PLS1):c.136C>T(p.Pro46Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PLS1
NM_001145319.2 missense
NM_001145319.2 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.38
Genes affected
PLS1 (HGNC:9090): (plastin 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The protein encoded by this gene is a third distinct plastin isoform, which is specifically expressed at high levels in the small intestine. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Feb 2010]
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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=0.30486226).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS1 | NM_001145319.2 | c.136C>T | p.Pro46Ser | missense_variant | 3/16 | ENST00000457734.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS1 | ENST00000457734.7 | c.136C>T | p.Pro46Ser | missense_variant | 3/16 | 2 | NM_001145319.2 | P1 | |
ENST00000690164.1 | n.119-12249G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T;T;T;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;L;.;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;D;D;D;N;D;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
B;.;.;.;.;B;.;B
Vest4
MutPred
Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);Loss of ubiquitination at K51 (P = 0.0637);
MVP
MPC
0.77
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at