3-142683985-CT-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001145319.2(PLS1):c.580-11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,143,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 3-142683985-CT-C is Benign according to our data. Variant chr3-142683985-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3056069.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS1	NM_001145319.2	c.580-11del		intron_variant		ENST00000457734.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS1	ENST00000457734.7	c.580-11del		intron_variant		2	NM_001145319.2	P1
	ENST00000690164.1	n.119-26780del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 147470 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00597 AC: 6830 AN: 1143190 Hom.: 0 Cov.: 27 AF XY: 0.00626 AC XY: 3542 AN XY: 566168

Gnomad4 AFR exome AF: 0.00544

Gnomad4 AMR exome AF: 0.00847

Gnomad4 ASJ exome AF: 0.00841

Gnomad4 EAS exome AF: 0.00259

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.00411

Gnomad4 NFE exome AF: 0.00562

Gnomad4 OTH exome AF: 0.00626

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000678 AC: 10 AN: 147540 Hom.: 0 Cov.: 32 AF XY: 0.0000557 AC XY: 4 AN XY: 71818

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000104

Gnomad4 NFE AF: 0.000135

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0225 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLS1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 14, 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: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753266465; hg19: chr3-142402827;