X-115622116-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005032.7(PLS3):c.74-130T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 519,785 control chromosomes in the GnomAD database, including 58 homozygotes. There are 760 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (42 hom., 538 hem., cov: 24)
  • Exomes 𝑓: 0.0024 (16 hom. 222 hem.)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-115622116-T-A is Benign according to our data. Variant chrX-115622116-T-A is described in ClinVar as [Benign]. Clinvar id is 1287469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS3	NM_005032.7	c.74-130T>A		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.74-130T>A		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 1914 AN: 112105 Hom.: 42 Cov.: 24 AF XY: 0.0157 AC XY: 538 AN XY: 34301

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00264

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.00238 AC: 971 AN: 407628 Hom.: 16 Cov.: 6 AF XY: 0.00182 AC XY: 222 AN XY: 121696

Gnomad4 AFR exome AF: 0.0604

Gnomad4 AMR exome AF: 0.00759

Gnomad4 ASJ exome AF: 0.00158

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.0000283

Gnomad4 NFE exome AF: 0.000328

Gnomad4 OTH exome AF: 0.00593

GnomAD4 genome AF: 0.0171 AC: 1916 AN: 112157 Hom.: 42 Cov.: 24 AF XY: 0.0157 AC XY: 538 AN XY: 34363

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00264

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000413

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0135 Hom.: 42

Bravo AF: 0.0209

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

Aug 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.8
Dann	Benign	0.71

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: rs113228979; hg19: chrX-114856428;