X-115622010-A-G

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.74-236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 317,733 control chromosomes in the GnomAD database, including 238 homozygotes. There are 1,379 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 (203 hom., 1129 hem., cov: 23)
  • Exomes 𝑓: 0.0050 (35 hom. 250 hem.)
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890

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=-0.89).
• BP6: Variant X-115622010-A-G is Benign according to our data. Variant chrX-115622010-A-G is described in ClinVar as [Benign]. Clinvar id is 1259784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS3	NM_005032.7	c.74-236A>G		intron_variant		ENST00000355899.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS3	ENST00000355899.8	c.74-236A>G		intron_variant		1	NM_005032.7	P1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 4212 AN: 111754 Hom.: 203 Cov.: 23 AF XY: 0.0329 AC XY: 1116 AN XY: 33928

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00406

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.0260

GnomAD4 exome AF: 0.00504 AC: 1037 AN: 205923 Hom.: 35 Cov.: 0 AF XY: 0.00487 AC XY: 250 AN XY: 51367

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.00864

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00512

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0378 AC: 4228 AN: 111810 Hom.: 203 Cov.: 23 AF XY: 0.0332 AC XY: 1129 AN XY: 33994

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00407

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.0276

Alfa AF: 0.0296 Hom.: 94

Bravo AF: 0.0440

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	-0.89
Cadd	Benign	0.41
Dann	Benign	0.63

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: rs114536525; hg19: chrX-114856322;