rs871773

Variant names:

• chrX-115646203-C-T
• rs871773
• NM_005032.7:c.1377+17C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-115646203-C-T
• chrX-115646203-C-A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.585
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• X-linked osteoporosis with fractures

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hernia, anterior diaphragmatic

  Inheritance: XL Classification: MODERATE Submitted by: Baylor College of Medicine Research Center

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 516191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005032.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3	NM_005032.7	MANE Select	c.1377+17C>T		intron	N/A	NP_005023.2
	PLS3	NM_001136025.5		c.1377+17C>T		intron	N/A	NP_001129497.1	P13797-1
	PLS3	NM_001440791.1		c.1377+17C>T		intron	N/A	NP_001427720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3	ENST00000355899.8	TSL:1 MANE Select	c.1377+17C>T		intron	N/A	ENSP00000348163.3	P13797-1
	PLS3	ENST00000539310.5	TSL:1	c.1377+17C>T		intron	N/A	ENSP00000445339.2	P13797-1
	PLS3	ENST00000969759.1		c.1425+17C>T		intron	N/A	ENSP00000639818.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16345 AN: 110992 Hom.: 2027 Cov.: 23

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

GnomAD2 exomes AF: 0.0738 AC: 11016 AN: 149314 AF XY: 0.0666

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 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

African (AFR) AF: 0.443 AC: 9136 AN: 20631

American (AMR) AF: 0.0488 AC: 1485 AN: 30420

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 673 AN: 16825

East Asian (EAS) AF: 0.0361 AC: 1040 AN: 28787

South Asian (SAS) AF: 0.0986 AC: 4434 AN: 44965

European-Finnish (FIN) AF: 0.0400 AC: 1585 AN: 39655

Middle Eastern (MID) AF: 0.0520 AC: 183 AN: 3521

European-Non Finnish (NFE) AF: 0.0309 AC: 19109 AN: 618142

Other (OTH) AF: 0.0705 AC: 2623 AN: 37226

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

African (AFR) AF: 0.420 AC: 12755 AN: 30381

American (AMR) AF: 0.0877 AC: 909 AN: 10370

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 122 AN: 2638

East Asian (EAS) AF: 0.0476 AC: 169 AN: 3550

South Asian (SAS) AF: 0.0876 AC: 230 AN: 2627

European-Finnish (FIN) AF: 0.0388 AC: 231 AN: 5957

Middle Eastern (MID) AF: 0.0734 AC: 16 AN: 218

European-Non Finnish (NFE) AF: 0.0332 AC: 1764 AN: 53102

Other (OTH) AF: 0.133 AC: 202 AN: 1516

Alfa AF: 0.0872 Hom.: 766

Bravo AF: 0.166

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs871773; hg19: chrX-114880523;