chrX-115610306-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005032.7(PLS3):āc.56A>Gā(p.Glu19Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000973 in 1,027,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 23)
Exomes š: 9.7e-7 ( 0 hom. 0 hem. )
Consequence
PLS3
NM_005032.7 missense
NM_005032.7 missense
Scores
7
5
Clinical Significance
Conservation
PhyloP100: 5.16
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS3 | NM_005032.7 | c.56A>G | p.Glu19Gly | missense_variant | 2/16 | ENST00000355899.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS3 | ENST00000355899.8 | c.56A>G | p.Glu19Gly | missense_variant | 2/16 | 1 | NM_005032.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 9.73e-7 AC: 1AN: 1027916Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 305680
GnomAD4 exome
AF:
AC:
1
AN:
1027916
Hom.:
Cov.:
20
AF XY:
AC XY:
0
AN XY:
305680
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
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 | Jan 26, 2022 | The c.56A>G (p.E19G) alteration is located in exon 2 (coding exon 1) of the PLS3 gene. This alteration results from a A to G substitution at nucleotide position 56, causing the glutamic acid (E) at amino acid position 19 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;D;D;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.64
.;P;P;.
Vest4
MutPred
Loss of methylation at K23 (P = 0.0575);Loss of methylation at K23 (P = 0.0575);Loss of methylation at K23 (P = 0.0575);Loss of methylation at K23 (P = 0.0575);
MVP
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
Publications
No publications associated with this variant yet.