chrX-115622360-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_005032.7(PLS3):c.188A>G(p.Asp63Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000074 in 1,081,657 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000074 ( 0 hom. 3 hem. )
Consequence
PLS3
NM_005032.7 missense
NM_005032.7 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 6.04
Genes affected
PLS3 (HGNC:9091): (plastin 3) 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. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). The C-terminal 570 amino acids of the T-plastin and L-plastin proteins are 83% identical. It contains a potential calcium-binding site near the N terminus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3757062).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS3 | NM_005032.7 | c.188A>G | p.Asp63Gly | missense_variant | 3/16 | ENST00000355899.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS3 | ENST00000355899.8 | c.188A>G | p.Asp63Gly | missense_variant | 3/16 | 1 | NM_005032.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome AF: 0.00000740 AC: 8AN: 1081657Hom.: 0 Cov.: 26 AF XY: 0.00000862 AC XY: 3AN XY: 348175
GnomAD4 exome
AF:
AC:
8
AN:
1081657
Hom.:
Cov.:
26
AF XY:
AC XY:
3
AN XY:
348175
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 01, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;T
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.
REVEL
Benign
Sift
Benign
T;.;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;B;.;.
Vest4
MutPred
Loss of ubiquitination at K59 (P = 0.0417);.;Loss of ubiquitination at K59 (P = 0.0417);Loss of ubiquitination at K59 (P = 0.0417);.;
MVP
MPC
1.0
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