X-115622196-C-A

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.74-50C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 1,024,046 control chromosomes in the GnomAD database, including 372 homozygotes. There are 2,219 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (209 hom., 1132 hem., cov: 23)
  • Exomes 𝑓: 0.0045 (163 hom. 1087 hem.)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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=-0.91).
• BP6: Variant X-115622196-C-A is Benign according to our data. Variant chrX-115622196-C-A is described in ClinVar as [Benign]. Clinvar id is 1243943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS3	NM_005032.7	c.74-50C>A		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.74-50C>A		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 4245 AN: 111812 Hom.: 209 Cov.: 23 AF XY: 0.0329 AC XY: 1120 AN XY: 33992

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00404

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.0286

GnomAD3 exomes AF: 0.0121 AC: 1875 AN: 155553 Hom.: 87 AF XY: 0.00794 AC XY: 383 AN XY: 48239

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.00677

Gnomad ASJ exome AF: 0.00287

Gnomad EAS exome AF: 0.0000852

Gnomad SAS exome AF: 0.00434

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000402

Gnomad OTH exome AF: 0.00655

GnomAD4 exome AF: 0.00449 AC: 4098 AN: 912182 Hom.: 163 Cov.: 14 AF XY: 0.00422 AC XY: 1087 AN XY: 257328

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.00835

Gnomad4 ASJ exome AF: 0.00202

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000198

Gnomad4 OTH exome AF: 0.00947

GnomAD4 genome AF: 0.0381 AC: 4260 AN: 111864 Hom.: 209 Cov.: 23 AF XY: 0.0332 AC XY: 1132 AN XY: 34054

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00368

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0201 Hom.: 106

Bravo AF: 0.0443

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	-0.91
Cadd	Benign	0.011
Dann	Benign	0.44

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: rs144675308; hg19: chrX-114856508;