rs6643869

Positions:

• chrX-115597455-G-A
• chrX-115597455-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005032.7(PLS3):​c.-8-12788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 110,794 control chromosomes in the GnomAD database, including 4,234 homozygotes. There are 10,182 hemizygotes in GnomAD. 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 0.30 (4234 hom., 10182 hem., cov: 23)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS3	NM_005032.7	c.-8-12788G>A		intron_variant		ENST00000355899.8	NP_005023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8	c.-8-12788G>A		intron_variant		1	NM_005032.7	ENSP00000348163.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 33342 AN: 110738 Hom.: 4233 Cov.: 23 AF XY: 0.309 AC XY: 10182 AN XY: 32972

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.301 AC: 33337 AN: 110794 Hom.: 4234 Cov.: 23 AF XY: 0.308 AC XY: 10182 AN XY: 33038

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.296

Alfa AF: 0.360 Hom.: 11486

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.55

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: rs6643869; hg19: chrX-114831767;