chrX-115622249-T-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005032.7(PLS3):c.77T>C(p.Leu26Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,194,174 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000019 ( 0 hom. 9 hem. )
Consequence
PLS3
NM_005032.7 missense
NM_005032.7 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 5.12
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 -4 ACMG points.
BS2
?
High Hemizygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS3 | NM_005032.7 | c.77T>C | p.Leu26Pro | missense_variant | 3/16 | ENST00000355899.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS3 | ENST00000355899.8 | c.77T>C | p.Leu26Pro | missense_variant | 3/16 | 1 | NM_005032.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000268 AC: 3AN: 111955Hom.: 0 Cov.: 23 AF XY: 0.0000587 AC XY: 2AN XY: 34091
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GnomAD4 exome AF: 0.0000194 AC: 21AN: 1082219Hom.: 0 Cov.: 26 AF XY: 0.0000257 AC XY: 9AN XY: 350803
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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 10, 2023 | The c.77T>C (p.L26P) alteration is located in exon 3 (coding exon 2) of the PLS3 gene. This alteration results from a T to C substitution at nucleotide position 77, causing the leucine (L) at amino acid position 26 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;T
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;.;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;P;.;.
Vest4
MutPred
Gain of disorder (P = 0.0348);.;Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);.;
MVP
MPC
1.8
ClinPred
D
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