chr6-28297982-A-G

Variant names:

• chr6-28297982-A-G
• NM_032507.4:c.860A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032507.4(PGBD1):​c.860A>G​(p.Lys287Arg) 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: 29)
• Consequence: PGBD1 NM_032507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048125803).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGBD1	NM_032507.4	MANE Select	c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	NP_115896.1	Q96JS3
	PGBD1	NM_001184743.2		c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	NP_001171672.1	Q96JS3
	PGBD1	NM_001386059.1		c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	NP_001372988.1	Q96JS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGBD1	ENST00000682144.1	MANE Select	c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	ENSP00000506997.1	Q96JS3
	PGBD1	ENST00000259883.3	TSL:1	c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	ENSP00000259883.3	Q96JS3
	PGBD1	ENST00000918204.1		c.860A>G	p.Lys287Arg	missense	Exon 6 of 7	ENSP00000588263.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.084
DANN	Benign	0.91
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.042
Sift	Benign	0.50	T
Sift4G	Benign	0.52	T
Polyphen		0.0040	B
Vest4		0.055
MutPred		0.28		Loss of ubiquitination at K287 (P = 0.0023)
MVP		0.26
ClinPred		0.035	T
GERP RS		-3.1
Varity_R		0.031
gMVP		0.040
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr6-28265759;