rs3800324

Positions:

• chr6-28296904-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_032507.4(PGBD1):​c.731G>A​(p.Gly244Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,613,996 control chromosomes in the GnomAD database, including 5,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G244R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.085 (774 hom., cov: 32)
  • Exomes 𝑓: 0.061 (4823 hom.)
• Consequence: PGBD1 NM_032507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGBD1	NM_032507.4	c.731G>A	p.Gly244Glu	missense_variant	5/7	ENST00000682144.1	NP_115896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGBD1	ENST00000682144.1	c.731G>A	p.Gly244Glu	missense_variant	5/7		NM_032507.4	ENSP00000506997.1
PGBD1	ENST00000259883.3	c.731G>A	p.Gly244Glu	missense_variant	5/7	1		ENSP00000259883.3

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12867 AN: 152110 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0750

GnomAD3 exomes AF: 0.0926 AC: 23281 AN: 251288 Hom.: 1767 AF XY: 0.0907 AC XY: 12312 AN XY: 135802

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.0663

Gnomad EAS exome AF: 0.307

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.0515

Gnomad NFE exome AF: 0.0471

Gnomad OTH exome AF: 0.0665

GnomAD4 exome AF: 0.0613 AC: 89633 AN: 1461766 Hom.: 4823 Cov.: 31 AF XY: 0.0632 AC XY: 45947 AN XY: 727198

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.0619

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0510

Gnomad4 NFE exome AF: 0.0431

Gnomad4 OTH exome AF: 0.0653

GnomAD4 genome AF: 0.0846 AC: 12885 AN: 152230 Hom.: 774 Cov.: 32 AF XY: 0.0864 AC XY: 6428 AN XY: 74434

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0550 Hom.: 724

Bravo AF: 0.0915

TwinsUK AF: 0.0369 AC: 137

ALSPAC AF: 0.0436 AC: 168

ESP6500AA AF: 0.113 AC: 498

ESP6500EA AF: 0.0476 AC: 409

ExAC AF: 0.0903 AC: 10963

Asia WGS AF: 0.123 AC: 427 AN: 3478

EpiCase AF: 0.0442

EpiControl AF: 0.0462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.071
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.0070	B
Vest4		0.041
ClinPred		0.00057	T
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -4

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

Publications

LitVar

Other links and lift over

dbSNP: rs3800324; hg19: chr6-28264681; COSMIC: COSV52551663;