1-248917297-C-A

Variant names:

• chr1-248917297-C-A
• rs777855537
• NM_170725.3:c.713C>A

Variant summary

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

The NM_170725.3(PGBD2):​c.713C>A​(p.Ala238Glu) 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. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A238P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGBD2 NM_170725.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 0 publications found

Genes affected

PGBD2 (HGNC:19399): (piggyBac transposable element derived 2) 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. The exact function of this gene is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.020961136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170725.3. 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
	PGBD2	NM_170725.3	MANE Select	c.713C>A	p.Ala238Glu	missense	Exon 3 of 3	NP_733843.1	Q6P3X8-1
	PGBD2	NM_001017434.2		c.-41C>A		5_prime_UTR	Exon 3 of 3	NP_001017434.1	Q6P3X8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGBD2	ENST00000329291.6	TSL:1 MANE Select	c.713C>A	p.Ala238Glu	missense	Exon 3 of 3	ENSP00000331643.5	Q6P3X8-1
	PGBD2	ENST00000355360.8	TSL:1	c.-41C>A		5_prime_UTR	Exon 3 of 3	ENSP00000355424.3	Q6P3X8-2
	PGBD2	ENST00000935434.1		c.713C>A	p.Ala238Glu	missense	Exon 3 of 3	ENSP00000605493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
DANN	Benign	0.83
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.68
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.31		Gain of disorder (P = 0.0283)
MVP		0.014
MPC		0.059
ClinPred		0.033	T
GERP RS		2.9
Varity_R		0.069
gMVP		0.13
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs777855537; hg19: chr1-249211496;