chrX-115610310-C-T

Variant names:

• chrX-115610310-C-T
• rs1556635949
• NM_005032.7:c.60C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_005032.7(PLS3):​c.60C>T​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,022,991 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000039 (0 hom. 0 hem.)
• Consequence: PLS3 NM_005032.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09
• 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, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hernia, anterior diaphragmatic

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant X-115610310-C-T is Benign according to our data. Variant chrX-115610310-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3698776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.

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.60C>T	p.Ala20Ala	synonymous	Exon 2 of 16	NP_005023.2
	PLS3	NM_001136025.5		c.60C>T	p.Ala20Ala	synonymous	Exon 2 of 16	NP_001129497.1	P13797-1
	PLS3	NM_001440791.1		c.60C>T	p.Ala20Ala	synonymous	Exon 3 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.60C>T	p.Ala20Ala	synonymous	Exon 2 of 16	ENSP00000348163.3	P13797-1
	PLS3	ENST00000539310.5	TSL:1	c.60C>T	p.Ala20Ala	synonymous	Exon 2 of 16	ENSP00000445339.2	P13797-1
	PLS3	ENST00000489283.5	TSL:1	n.60C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000420458.1	F2Z2Z9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000122 AC: 2 AN: 164139 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000128

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000391 AC: 4 AN: 1022991 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 303327

African (AFR) AF: 0.00 AC: 0 AN: 24586

American (AMR) AF: 0.00 AC: 0 AN: 32149

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18500

East Asian (EAS) AF: 0.00 AC: 0 AN: 28932

South Asian (SAS) AF: 0.00 AC: 0 AN: 47106

European-Finnish (FIN) AF: 0.0000750 AC: 3 AN: 40024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3927

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 784294

Other (OTH) AF: 0.00 AC: 0 AN: 43473

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely 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	-0.30
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		1.1
PromoterAI		-0.044	Neutral

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

Other links and lift over

dbSNP: rs1556635949; hg19: chrX-114844622;