X-115610165-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.-8-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 434,879 control chromosomes in the GnomAD database, including 171 homozygotes. There are 1,293 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 (133 hom., 983 hem., cov: 23)
  • Exomes 𝑓: 0.0039 (38 hom. 310 hem.)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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=-0.85).
• BP6: Variant X-115610165-C-T is Benign according to our data. Variant chrX-115610165-C-T is described in ClinVar as [Benign]. Clinvar id is 1265980.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.-8-78C>T		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.-8-78C>T		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 3533 AN: 111382 Hom.: 133 Cov.: 23 AF XY: 0.0291 AC XY: 979 AN XY: 33644

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000745

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00427

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0232

GnomAD4 exome AF: 0.00391 AC: 1266 AN: 323447 Hom.: 38 AF XY: 0.00334 AC XY: 310 AN XY: 92795

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.00735

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000466

Gnomad4 SAS exome AF: 0.000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000167

Gnomad4 OTH exome AF: 0.00817

GnomAD4 genome AF: 0.0317 AC: 3537 AN: 111432 Hom.: 133 Cov.: 23 AF XY: 0.0292 AC XY: 983 AN XY: 33704

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0130

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: 0.0229

Alfa AF: 0.0241 Hom.: 71

Bravo AF: 0.0370

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.2
Dann	Benign	0.76

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: rs115844382; hg19: chrX-114844477;