chr3-142684133-T-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001145319.2(PLS1):c.707T>C(p.Val236Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00486 in 1,614,058 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0050 ( 18 hom. )
Consequence
PLS1
NM_001145319.2 missense
NM_001145319.2 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 4.78
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014731824).
BP6
?
Variant 3-142684133-T-C is Benign according to our data. Variant chr3-142684133-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2571191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 530 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS1 | NM_001145319.2 | c.707T>C | p.Val236Ala | missense_variant | 7/16 | ENST00000457734.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS1 | ENST00000457734.7 | c.707T>C | p.Val236Ala | missense_variant | 7/16 | 2 | NM_001145319.2 | P1 | |
ENST00000690164.1 | n.119-26927A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00348 AC: 530AN: 152158Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00309 AC: 776AN: 251224Hom.: 2 AF XY: 0.00303 AC XY: 412AN XY: 135780
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GnomAD4 exome AF: 0.00500 AC: 7315AN: 1461782Hom.: 18 Cov.: 32 AF XY: 0.00484 AC XY: 3519AN XY: 727184
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ESP6500AA
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43
ExAC
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336
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3478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PLS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | PLS1: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.;N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;B;B
Vest4
MVP
MPC
0.24
ClinPred
T
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