NM_005032.7:c.-8-21818T>C

Variant names:

• chrX-115588425-T-C
• rs2522188
• NM_005032.7:c.-8-21818T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005032.7(PLS3):​c.-8-21818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (18741 hom., 22842 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.-8-21818T>C		intron	N/A	NP_005023.2
	PLS3	NM_001282337.2		c.-193-21818T>C		intron	N/A	NP_001269266.1	P13797-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3	ENST00000355899.8	TSL:1 MANE Select	c.-8-21818T>C		intron	N/A	ENSP00000348163.3	P13797-1
	PLS3	ENST00000489283.5	TSL:1	n.-8-21818T>C		intron	N/A	ENSP00000420458.1	F2Z2Z9
	PLS3	ENST00000969759.1		c.-8-21818T>C		intron	N/A	ENSP00000639818.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 75843 AN: 111175 Hom.: 18733 Cov.: 24

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.682 AC: 75902 AN: 111225 Hom.: 18741 Cov.: 24 AF XY: 0.683 AC XY: 22842 AN XY: 33451

African (AFR) AF: 0.860 AC: 26407 AN: 30690

American (AMR) AF: 0.607 AC: 6340 AN: 10445

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 1663 AN: 2636

East Asian (EAS) AF: 0.454 AC: 1601 AN: 3530

South Asian (SAS) AF: 0.706 AC: 1864 AN: 2640

European-Finnish (FIN) AF: 0.714 AC: 4195 AN: 5872

Middle Eastern (MID) AF: 0.523 AC: 112 AN: 214

European-Non Finnish (NFE) AF: 0.614 AC: 32572 AN: 53022

Other (OTH) AF: 0.653 AC: 981 AN: 1502

Alfa AF: 0.634 Hom.: 36992

Bravo AF: 0.681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2522188; hg19: chrX-114822737;