3-142676221-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001145319.2(PLS1):c.429G>A(p.Lys143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
PLS1
NM_001145319.2 synonymous
NM_001145319.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.123
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 3-142676221-G-A is Benign according to our data. Variant chr3-142676221-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3036686.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.123 with no splicing effect.
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLS1 | NM_001145319.2 | c.429G>A | p.Lys143= | synonymous_variant | 5/16 | ENST00000457734.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLS1 | ENST00000457734.7 | c.429G>A | p.Lys143= | synonymous_variant | 5/16 | 2 | NM_001145319.2 | P1 | |
ENST00000690164.1 | n.119-19015C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152162
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251182Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135756
GnomAD3 exomes
AF:
AC:
8
AN:
251182
Hom.:
AF XY:
AC XY:
4
AN XY:
135756
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460700Hom.: 0 Cov.: 29 AF XY: 0.0000261 AC XY: 19AN XY: 726706
GnomAD4 exome
AF:
AC:
38
AN:
1460700
Hom.:
Cov.:
29
AF XY:
AC XY:
19
AN XY:
726706
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 ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74326
GnomAD4 genome
?
AF:
AC:
2
AN:
152162
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74326
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PLS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 09, 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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