chrX-115646203-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005032.7(PLS3):c.1377+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 951,215 control chromosomes in the GnomAD database, including 4,224 homozygotes. There are 16,671 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 2035 hom., 4608 hem., cov: 23)
Exomes 𝑓: 0.048 ( 2189 hom. 12063 hem. )
Consequence
PLS3
NM_005032.7 intron
NM_005032.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.585
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant X-115646203-C-T is Benign according to our data. Variant chrX-115646203-C-T is described in ClinVar as [Benign]. Clinvar id is 516191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-115646203-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS3 | NM_005032.7 | c.1377+17C>T | intron_variant | ENST00000355899.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS3 | ENST00000355899.8 | c.1377+17C>T | intron_variant | 1 | NM_005032.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.147 AC: 16345AN: 110992Hom.: 2027 Cov.: 23 AF XY: 0.137 AC XY: 4573AN XY: 33266
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GnomAD3 exomes AF: 0.0738 AC: 11016AN: 149314Hom.: 1009 AF XY: 0.0666 AC XY: 2849AN XY: 42750
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GnomAD4 exome AF: 0.0479 AC: 40268AN: 840172Hom.: 2189 Cov.: 14 AF XY: 0.0554 AC XY: 12063AN XY: 217882
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GnomAD4 genome AF: 0.148 AC: 16401AN: 111043Hom.: 2035 Cov.: 23 AF XY: 0.138 AC XY: 4608AN XY: 33327
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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