X-115622304-T-G

Variant names:

• chrX-115622304-T-G
• rs782750342
• NM_005032.7:c.132T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005032.7(PLS3):​c.132T>G​(p.Ala44Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,066,923 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000022 (0 hom. 9 hem.)
• Consequence: PLS3 NM_005032.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.104
• Publications: 0 publications found

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]

PLS3 Gene-Disease associations (from GenCC):

• X-linked osteoporosis with fractures

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• hernia, anterior diaphragmatic

  Inheritance: XL Classification: MODERATE Submitted by: Baylor College of Medicine Research Center

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-115622304-T-G is Benign according to our data. Variant chrX-115622304-T-G is described in ClinVar as Benign. ClinVar VariationId is 2044534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 9 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005032.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3	NM_005032.7	MANE Select	c.132T>G	p.Ala44Ala	synonymous	Exon 3 of 16	NP_005023.2
	PLS3	NM_001136025.5		c.132T>G	p.Ala44Ala	synonymous	Exon 3 of 16	NP_001129497.1	P13797-1
	PLS3	NM_001440791.1		c.132T>G	p.Ala44Ala	synonymous	Exon 4 of 17	NP_001427720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS3	ENST00000355899.8	TSL:1 MANE Select	c.132T>G	p.Ala44Ala	synonymous	Exon 3 of 16	ENSP00000348163.3	P13797-1
	PLS3	ENST00000539310.5	TSL:1	c.132T>G	p.Ala44Ala	synonymous	Exon 3 of 16	ENSP00000445339.2	P13797-1
	PLS3	ENST00000489283.5	TSL:1	n.*385T>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000420458.1	F2Z2Z9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000617 AC: 11 AN: 178388 AF XY: 0.0000791

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000746

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000225 AC: 24 AN: 1066923 Hom.: 0 Cov.: 24 AF XY: 0.0000269 AC XY: 9 AN XY: 334331

African (AFR) AF: 0.00 AC: 0 AN: 25813

American (AMR) AF: 0.00 AC: 0 AN: 34829

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19121

East Asian (EAS) AF: 0.0000334 AC: 1 AN: 29898

South Asian (SAS) AF: 0.00 AC: 0 AN: 52347

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.0000233 AC: 19 AN: 815305

Other (OTH) AF: 0.0000666 AC: 3 AN: 45048

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.5
DANN	Benign	0.53
PhyloP100		-0.10
Mutation Taster		=295/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782750342; hg19: chrX-114856616;