rs5987755

Variant names:

• chrX-115611942-C-T
• rs5987755
• NM_005032.7:c.73+1619C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005032.7(PLS3):​c.73+1619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 111,293 control chromosomes in the GnomAD database, including 1 homozygotes. There are 118 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 0.0035 (1 hom., 118 hem., cov: 23)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00347 (386/111293) while in subpopulation AFR AF= 0.012 (368/30773). AF 95% confidence interval is 0.011. There are 1 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 118 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS3	NM_005032.7	c.73+1619C>T		intron_variant	Intron 2 of 15	ENST00000355899.8	NP_005023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8	c.73+1619C>T		intron_variant	Intron 2 of 15	1	NM_005032.7	ENSP00000348163.3

Frequencies

GnomAD3 genomes AF: 0.00347 AC: 386 AN: 111242 Hom.: 1 Cov.: 23 AF XY: 0.00352 AC XY: 118 AN XY: 33492

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000670

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000381

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000378

Gnomad OTH AF: 0.00334

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

GnomAD4 genome AF: 0.00347 AC: 386 AN: 111293 Hom.: 1 Cov.: 23 AF XY: 0.00352 AC XY: 118 AN XY: 33553

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.000669

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000383

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000378

Gnomad4 OTH AF: 0.00330

Alfa AF: 0.00371 Hom.: 10

Bravo AF: 0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.41

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: rs5987755; hg19: chrX-114846254;