Genetic Variant PLS3:c.-8-139G>A (chrX-115610104-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005032.7(PLS3):c.-8-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 305,013 control chromosomes in the GnomAD database, including 35 homozygotes. There are 622 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 33 hom., 500 hem., cov: 23)

Exomes 𝑓: 0.0024 ( 2 hom. 122 hem. )

Consequence

PLS3
NM_005032.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.857

Variant links:

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]

PLS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-115610104-G-A is Benign according to our data. Variant chrX-115610104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196403.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS3	NM_005032.7 link	c.-8-139G>A		intron_variant	Intron 1 of 15	ENST00000355899.8	NP_005023.2	P13797-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8 link	c.-8-139G>A		intron_variant	Intron 1 of 15	1	NM_005032.7	ENSP00000348163.3		P13797-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

1731

AN:

112098

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

496

AN XY:

34300

show subpopulations

Gnomad AFR

AF:

0.0531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000320

Gnomad OTH

AF:

0.0112

GnomAD4 exome

AF:

0.00244

AC:

470

AN:

192860

Hom.:

AF XY:

0.00215

AC XY:

122

AN XY:

56820

show subpopulations

Gnomad4 AFR exome

AF:

0.0544

Gnomad4 AMR exome

AF:

0.00488

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000873

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000380

Gnomad4 OTH exome

AF:

0.00610

GnomAD4 genome

AF:

0.0155

AC:

1735

AN:

112153

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

500

AN XY:

34365

show subpopulations

Gnomad4 AFR

AF:

0.0532

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000368

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000320

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.19

DANN

Benign

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over