chrX-115610487-CT-C

Position:

• chrX-115610487-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005032.7(PLS3):​c.73+178del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 93,920 control chromosomes in the GnomAD database, including 6 homozygotes. There are 125 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0090 (6 hom., 125 hem., cov: 21)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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 -10 ACMG points.

• BP6: Variant X-115610487-CT-C is Benign according to our data. Variant chrX-115610487-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1186573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00899 (844/93920) while in subpopulation AFR AF= 0.024 (629/26259). AF 95% confidence interval is 0.0224. There are 6 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS3	NM_005032.7	c.73+178del		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.73+178del		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.00900 AC: 845 AN: 93930 Hom.: 6 Cov.: 21 AF XY: 0.00508 AC XY: 125 AN XY: 24600

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00416

Gnomad ASJ AF: 0.00349

Gnomad EAS AF: 0.000669

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00883

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

GnomAD4 genome AF: 0.00899 AC: 844 AN: 93920 Hom.: 6 Cov.: 21 AF XY: 0.00508 AC XY: 125 AN XY: 24600

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.00416

Gnomad4 ASJ AF: 0.00349

Gnomad4 EAS AF: 0.000672

Gnomad4 SAS AF: 0.00141

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00872

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs368406135; hg19: chrX-114844799;