rs1017191400

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005032.7(PLS3):c.77T>A(p.Leu26His) variant causes a missense change. The variant allele was found at a frequency of 0.00000893 in 111,955 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L26P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

PLS3
NM_005032.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.12

Publications

0 publications found

Variant links:

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

PLS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLS3	NM_005032.7	MANE Select	c.77T>A	p.Leu26His	missense	Exon 3 of 16	NP_005023.2
PLS3	NM_001136025.5		c.77T>A	p.Leu26His	missense	Exon 3 of 16	NP_001129497.1	P13797-1
PLS3	NM_001440791.1		c.77T>A	p.Leu26His	missense	Exon 4 of 17	NP_001427720.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLS3	ENST00000355899.8	TSL:1 MANE Select	c.77T>A	p.Leu26His	missense	Exon 3 of 16	ENSP00000348163.3	P13797-1
PLS3	ENST00000539310.5	TSL:1	c.77T>A	p.Leu26His	missense	Exon 3 of 16	ENSP00000445339.2	P13797-1
PLS3	ENST00000489283.5	TSL:1	n.*330T>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000420458.1	F2Z2Z9

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111955

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.24e-7

AC:

AN:

1082219

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

350803

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25803

American (AMR)

AF:

0.00

AC:

AN:

32330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19032

East Asian (EAS)

AF:

0.00

AC:

AN:

29783

South Asian (SAS)

AF:

0.00

AC:

AN:

49762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

835401

Other (OTH)

AF:

0.00

AC:

AN:

45544

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111955

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34091

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30843

American (AMR)

AF:

0.00

AC:

AN:

10480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00

AC:

AN:

2699

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53200

Other (OTH)

AF:

0.00

AC:

AN:

1502

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.33

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.3

PhyloP100

5.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.6

REVEL

Benign

0.28

Sift

Benign

0.12

Sift4G

Benign

0.098

Polyphen

0.86

Vest4

0.48

MutPred

0.36

Gain of disorder (P = 0.041)

MVP

0.82

MPC

1.8

ClinPred

0.88

GERP RS

5.4

Varity_R

0.34

gMVP

0.75

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over