6-28300890-G-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032507.4(PGBD1):​c.1036G>A​(p.Asp346Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,614,108 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0038 ( 22 hom. )

Consequence

PGBD1
NM_032507.4 missense

Scores

1
6
11

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.10
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.006383151).
BP6
Variant 6-28300890-G-A is Benign according to our data. Variant chr6-28300890-G-A is described in ClinVar as [Benign]. Clinvar id is 773194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PGBD1NM_032507.4 linkc.1036G>A p.Asp346Asn missense_variant Exon 7 of 7 ENST00000682144.1 NP_115896.1 Q96JS3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PGBD1ENST00000682144.1 linkc.1036G>A p.Asp346Asn missense_variant Exon 7 of 7 NM_032507.4 ENSP00000506997.1 Q96JS3
PGBD1ENST00000259883.3 linkc.1036G>A p.Asp346Asn missense_variant Exon 7 of 7 1 ENSP00000259883.3 Q96JS3

Frequencies

GnomAD3 genomes
AF:
0.00452
AC:
687
AN:
152112
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000652
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0131
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0130
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00426
Gnomad OTH
AF:
0.00478
GnomAD2 exomes
AF:
0.00477
AC:
1198
AN:
250978
AF XY:
0.00442
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0103
Gnomad ASJ exome
AF:
0.00805
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0121
Gnomad NFE exome
AF:
0.00392
Gnomad OTH exome
AF:
0.00424
GnomAD4 exome
AF:
0.00382
AC:
5579
AN:
1461878
Hom.:
22
Cov.:
35
AF XY:
0.00380
AC XY:
2767
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
AC:
16
AN:
33480
Gnomad4 AMR exome
AF:
0.0120
AC:
536
AN:
44720
Gnomad4 ASJ exome
AF:
0.00815
AC:
213
AN:
26136
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39698
Gnomad4 SAS exome
AF:
0.000730
AC:
63
AN:
86258
Gnomad4 FIN exome
AF:
0.00975
AC:
521
AN:
53418
Gnomad4 NFE exome
AF:
0.00363
AC:
4033
AN:
1112004
Gnomad4 Remaining exome
AF:
0.00325
AC:
196
AN:
60396
Heterozygous variant carriers
0
366
733
1099
1466
1832
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
146
292
438
584
730
<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:
0.00455
AC:
693
AN:
152230
Hom.:
6
Cov.:
32
AF XY:
0.00533
AC XY:
397
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.000650
AC:
0.000650195
AN:
0.000650195
Gnomad4 AMR
AF:
0.0135
AC:
0.0134729
AN:
0.0134729
Gnomad4 ASJ
AF:
0.00605
AC:
0.00605187
AN:
0.00605187
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000207
AC:
0.000207039
AN:
0.000207039
Gnomad4 FIN
AF:
0.0130
AC:
0.0130164
AN:
0.0130164
Gnomad4 NFE
AF:
0.00426
AC:
0.00426383
AN:
0.00426383
Gnomad4 OTH
AF:
0.00473
AC:
0.0047259
AN:
0.0047259
Heterozygous variant carriers
0
39
78
118
157
196
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00420
Hom.:
6
Bravo
AF:
0.00414
TwinsUK
AF:
0.00378
AC:
14
ALSPAC
AF:
0.00493
AC:
19
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00430
AC:
37
ExAC
AF:
0.00410
AC:
498
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00365
EpiControl
AF:
0.00296

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PGBD1: BS1, BS2 -

Dec 13, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.67
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.028
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.78
T
MetaRNN
Benign
0.0064
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.077
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.049
D
Polyphen
0.98
D
Vest4
0.22
MVP
0.37
ClinPred
0.018
T
GERP RS
4.5
Varity_R
0.085
gMVP
0.28
Mutation Taster
=100/0
polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148252586; hg19: chr6-28268667; COSMIC: COSV105012383; API