Genetic Variant PGBD1:p.Val262Glu (chr6-28297907-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032507.4(PGBD1):c.785T>A(p.Val262Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000198 in 1,515,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PGBD1
NM_032507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.707

Publications

0 publications found

Variant links:

Genes affected

PGBD1 (HGNC:19398): (piggyBac transposable element derived 1) The piggyBac family of proteins, found in diverse animals, are transposases related to the transposase of the canonical piggyBac transposon from the moth, Trichoplusia ni. This family also includes genes in several genomes, including human, that appear to have been derived from the piggyBac transposons. This gene belongs to the subfamily of piggyBac transposable element derived (PGBD) genes. The PGBD proteins appear to be novel, with no obvious relationship to other transposases, or other known protein families. This gene product is specifically expressed in the brain, however, its exact function is not known. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2010]

PGBD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13787785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGBD1	NM_032507.4	MANE Select	c.785T>A	p.Val262Glu	missense	Exon 6 of 7	NP_115896.1	Q96JS3
PGBD1	NM_001184743.2		c.785T>A	p.Val262Glu	missense	Exon 6 of 7	NP_001171672.1	Q96JS3
PGBD1	NM_001386059.1		c.785T>A	p.Val262Glu	missense	Exon 6 of 7	NP_001372988.1	Q96JS3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGBD1	ENST00000682144.1	MANE Select	c.785T>A	p.Val262Glu	missense	Exon 6 of 7	ENSP00000506997.1	Q96JS3
PGBD1	ENST00000259883.3	TSL:1	c.785T>A	p.Val262Glu	missense	Exon 6 of 7	ENSP00000259883.3	Q96JS3
PGBD1	ENST00000918204.1		c.785T>A	p.Val262Glu	missense	Exon 6 of 7	ENSP00000588263.1

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147712

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244872

AF XY:

0.00000754

show subpopulations

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:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1367628

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682260

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29588

American (AMR)

AF:

0.00

AC:

AN:

40930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23856

East Asian (EAS)

AF:

0.00

AC:

AN:

35100

South Asian (SAS)

AF:

0.00

AC:

AN:

82922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1044566

Other (OTH)

AF:

0.00

AC:

AN:

55312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.00000677

AC:

AN:

147712

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39690

American (AMR)

AF:

0.00

AC:

AN:

14562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.00

AC:

AN:

4600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67406

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000142

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.47

M_CAP

Benign

0.0041

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

PhyloP100

0.71

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.36

REVEL

Benign

0.059

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

0.84

Vest4

0.33

MutPred

0.28

Loss of catalytic residue at V262 (P = 0.0651)

MVP

0.25

ClinPred

0.39

GERP RS

2.0

Varity_R

0.39

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over