rs871773

chrX-115646203-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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]

ACMG classification

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: 16345 AN: 110992 Hom.: 2027 Cov.: 23 AF XY: 0.137 AC XY: 4573 AN XY: 33266

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0667

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.0738 AC: 11016 AN: 149314 Hom.: 1009 AF XY: 0.0666 AC XY: 2849 AN XY: 42750

Gnomad AFR exome AF: 0.439

Gnomad AMR exome AF: 0.0423

Gnomad ASJ exome AF: 0.0405

Gnomad EAS exome AF: 0.0557

Gnomad SAS exome AF: 0.0971

Gnomad FIN exome AF: 0.0393

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0589

GnomAD4 exome AF: 0.0479 AC: 40268 AN: 840172 Hom.: 2189 Cov.: 14 AF XY: 0.0554 AC XY: 12063 AN XY: 217882

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.0488

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.0361

Gnomad4 SAS exome AF: 0.0986

Gnomad4 FIN exome AF: 0.0400

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0705

GnomAD4 genome AF: 0.148 AC: 16401 AN: 111043 Hom.: 2035 Cov.: 23 AF XY: 0.138 AC XY: 4608 AN XY: 33327

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.0462

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0872 Hom.: 766

Bravo AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.2
Dann	Benign	0.55

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: rs871773; hg19: chrX-114880523;