dbSNP rs757124: PLS3:n.-55G>C (chrX-115561214-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000489283.5(PLS3):n.-55G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 15473 hom., 20861 hem., cov: 23)

Exomes 𝑓: 0.55 ( 6 hom. 16 hem. )

Failed GnomAD Quality Control

Consequence

PLS3
ENST00000489283.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.872

Publications

7 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 links:

PLS3-AS1 (HGNC:50343): (PLS3 antisense RNA 1)

PLS3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000489283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLS3	NM_005032.7	MANE Select	c.-55G>C	5_prime_UTR	Exon 1 of 16	NP_005023.2
PLS3	NM_001282337.2		c.-240G>C	5_prime_UTR	Exon 1 of 18	NP_001269266.1
PLS3-AS1	NR_110383.1		n.233+1190C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLS3	ENST00000489283.5	TSL:1	n.-55G>C	non_coding_transcript_exon	Exon 1 of 6	ENSP00000420458.1
PLS3	ENST00000355899.8	TSL:1 MANE Select	c.-55G>C	5_prime_UTR	Exon 1 of 16	ENSP00000348163.3
PLS3	ENST00000489283.5	TSL:1	n.-55G>C	5_prime_UTR	Exon 1 of 6	ENSP00000420458.1

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

69487

AN:

111004

Hom.:

15466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.653

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.624

GnomAD4 exome

AF:

0.552

AC:

AN:

Hom.:

Cov.:

AF XY:

0.552

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.626

AC:

69544

AN:

111056

Hom.:

15473

Cov.:

AF XY:

0.627

AC XY:

20861

AN XY:

33286

show subpopulations

African (AFR)

AF:

0.733

AC:

22385

AN:

30531

American (AMR)

AF:

0.577

AC:

6086

AN:

10556

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

1709

AN:

2631

East Asian (EAS)

AF:

0.536

AC:

1855

AN:

3463

South Asian (SAS)

AF:

0.656

AC:

1716

AN:

2614

European-Finnish (FIN)

AF:

0.653

AC:

3891

AN:

5957

Middle Eastern (MID)

AF:

0.521

AC:

111

AN:

213

European-Non Finnish (NFE)

AF:

0.579

AC:

30634

AN:

52917

Other (OTH)

AF:

0.626

AC:

943

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

934

1868

2802

3736

4670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.406

Hom.:

1666

Bravo

AF:

0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

PhyloP100

0.87

PromoterAI

0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over