3-142671067-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001145319.2(PLS1):c.309T>G(p.Thr103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00762 in 1,607,576 control chromosomes in the GnomAD database, including 516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (461 hom.)
• Consequence: PLS1 NM_001145319.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.265

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-142671067-T-G is Benign according to our data. Variant chr3-142671067-T-G is described in ClinVar as [Benign]. Clinvar id is 1253042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.265 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS1	NM_001145319.2	c.309T>G	p.Thr103=	synonymous_variant	4/16	ENST00000457734.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS1	ENST00000457734.7	c.309T>G	p.Thr103=	synonymous_variant	4/16	2	NM_001145319.2	P1
	ENST00000690164.1	n.119-13861A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1638 AN: 152232 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.0211 AC: 5289 AN: 250702 Hom.: 390 AF XY: 0.0162 AC XY: 2195 AN XY: 135492

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00237

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00394

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.00728 AC: 10592 AN: 1455226 Hom.: 461 Cov.: 27 AF XY: 0.00654 AC XY: 4737 AN XY: 724308

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.000974

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00663

GnomAD4 genome AF: 0.0109 AC: 1657 AN: 152350 Hom.: 55 Cov.: 32 AF XY: 0.0116 AC XY: 865 AN XY: 74504

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00472

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00315 Hom.: 2

Bravo AF: 0.0178

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00333

EpiControl AF: 0.00403

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	7.5
Dann	Benign	0.80

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: rs148556280; hg19: chr3-142389909;