ENST00000606397.1:n.209+1556A>C

Variant names:

• chrX-115560848-T-G
• rs1557770
• ENST00000606397.1:n.209+1556A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000606397.1(PLS3-AS1):​n.209+1556A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 111,250 control chromosomes in the GnomAD database, including 9,106 homozygotes. There are 15,765 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 0.47 (9106 hom., 15765 hem., cov: 24)
• Consequence: PLS3-AS1 ENST00000606397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• Publications: 2 publications found

Genes affected

PLS3-AS1 (HGNC:50343): (PLS3 antisense RNA 1)

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• hernia, anterior diaphragmatic

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606397.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3-AS1	NR_110383.1		n.233+1556A>C		intron	N/A
	PLS3-AS1	NR_110384.1		n.233+1556A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3-AS1	ENST00000606397.1	TSL:4	n.209+1556A>C		intron	N/A
	PLS3-AS1	ENST00000607680.5	TSL:2	n.233+1556A>C		intron	N/A
	PLS3	ENST00000876571.1		c.-421T>G		upstream_gene	N/A	ENSP00000546630.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 51739 AN: 111196 Hom.: 9105 Cov.: 24

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.465 AC: 51748 AN: 111250 Hom.: 9106 Cov.: 24 AF XY: 0.471 AC XY: 15765 AN XY: 33470

African (AFR) AF: 0.236 AC: 7282 AN: 30798

American (AMR) AF: 0.493 AC: 5202 AN: 10547

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 1557 AN: 2635

East Asian (EAS) AF: 0.506 AC: 1763 AN: 3483

South Asian (SAS) AF: 0.592 AC: 1551 AN: 2619

European-Finnish (FIN) AF: 0.634 AC: 3716 AN: 5863

Middle Eastern (MID) AF: 0.458 AC: 99 AN: 216

European-Non Finnish (NFE) AF: 0.560 AC: 29615 AN: 52900

Other (OTH) AF: 0.496 AC: 754 AN: 1520

Alfa AF: 0.530 Hom.: 61806

Bravo AF: 0.445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
PhyloP100		0.52
PromoterAI		0.037	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1557770; hg19: chrX-114795175;