X-115610223-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005032.7(PLS3):c.-8-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 927,014 control chromosomes in the GnomAD database, including 231 homozygotes. There are 1,607 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (134 hom., 966 hem., cov: 23)
  • Exomes 𝑓: 0.0034 (97 hom. 641 hem.)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-115610223-C-T is Benign according to our data. Variant chrX-115610223-C-T is described in ClinVar as [Benign]. Clinvar id is 516327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS3	NM_005032.7	c.-8-20C>T		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.-8-20C>T		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 3517 AN: 111143 Hom.: 134 Cov.: 23 AF XY: 0.0288 AC XY: 961 AN XY: 33419

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000747

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00948 AC: 1328 AN: 140045 Hom.: 50 AF XY: 0.00472 AC XY: 201 AN XY: 42559

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00482

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000254

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00573

GnomAD4 exome AF: 0.00340 AC: 2770 AN: 815820 Hom.: 97 Cov.: 12 AF XY: 0.00292 AC XY: 641 AN XY: 219762

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.00630

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000288

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000981

Gnomad4 OTH exome AF: 0.00658

GnomAD4 genome AF: 0.0317 AC: 3522 AN: 111194 Hom.: 134 Cov.: 23 AF XY: 0.0289 AC XY: 966 AN XY: 33480

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000374

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0231

Alfa AF: 0.0159 Hom.: 77

Bravo AF: 0.0370

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 01, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.079
Dann	Benign	0.20

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: rs114186394; hg19: chrX-114844535;