rs140121121

Positions:

chrX-115629281-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005032.7(PLS3):c.321T>A(p.Gly107Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,204,373 control chromosomes in the GnomAD database, including 145 homozygotes. There are 6,296 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 4 hom., 420 hem., cov: 23)

Exomes 𝑓: 0.017 ( 141 hom. 5876 hem. )

Consequence

PLS3
NM_005032.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.768

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-115629281-T-A is Benign according to our data. Variant chrX-115629281-T-A is described in ClinVar as [Benign]. Clinvar id is 88702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-115629281-T-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.768 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1382/111942) while in subpopulation NFE AF= 0.0184 (982/53243). AF 95% confidence interval is 0.0175. There are 4 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS3	NM_005032.7 link	c.321T>A	p.Gly107Gly	synonymous_variant	4/16	ENST00000355899.8	NP_005023.2	P13797-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8 link	c.321T>A	p.Gly107Gly	synonymous_variant	4/16	1	NM_005032.7	ENSP00000348163.3		P13797-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1381

AN:

111891

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

419

AN XY:

34059

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00326

Gnomad ASJ

AF:

0.00677

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00448

Gnomad FIN

AF:

0.0436

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.0147

AC:

2660

AN:

180425

Hom.:

AF XY:

0.0149

AC XY:

968

AN XY:

64991

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00471

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.0524

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0166

AC:

18125

AN:

1092431

Hom.:

141

Cov.:

AF XY:

0.0164

AC XY:

5876

AN XY:

358179

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00502

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00766

Gnomad4 FIN exome

AF:

0.0500

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0123

AC:

1382

AN:

111942

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

420

AN XY:

34120

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00326

Gnomad4 ASJ

AF:

0.00677

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00450

Gnomad4 FIN

AF:

0.0436

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.0152

Hom.:

113

Bravo

AF:

0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Bone mineral density quantitative trait locus 18

Benign:1Other:1

association, no assertion criteria provided	literature only	OMIM	Oct 17, 2013	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 26, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 29, 2018

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. -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.7

DANN

Benign

0.62

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