Genetic Variant PGBD1:p.Pro297Ser (chr6-28300743-C-T) – 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.889C>T(p.Pro297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PGBD1
NM_032507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.198

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:

Genome browser will be placed here

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=0.07691398).

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.889C>T	p.Pro297Ser	missense	Exon 7 of 7	NP_115896.1	Q96JS3
PGBD1	NM_001184743.2		c.889C>T	p.Pro297Ser	missense	Exon 7 of 7	NP_001171672.1	Q96JS3
PGBD1	NM_001386059.1		c.889C>T	p.Pro297Ser	missense	Exon 7 of 7	NP_001372988.1	Q96JS3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGBD1	ENST00000682144.1	MANE Select	c.889C>T	p.Pro297Ser	missense	Exon 7 of 7	ENSP00000506997.1	Q96JS3
PGBD1	ENST00000259883.3	TSL:1	c.889C>T	p.Pro297Ser	missense	Exon 7 of 7	ENSP00000259883.3	Q96JS3
PGBD1	ENST00000918204.1		c.889C>T	p.Pro297Ser	missense	Exon 7 of 7	ENSP00000588263.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.8

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.44

M_CAP

Benign

0.0043

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

PhyloP100

0.20

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.46

REVEL

Benign

0.0050

Sift

Benign

0.15

Sift4G

Benign

0.086

Polyphen

0.0060

Vest4

0.044

MutPred

0.25

Loss of catalytic residue at P297 (P = 0.0039)

MVP

0.34

ClinPred

0.037

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.15

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over