Genetic Variant NM_001099403.2:c.649_651delCAG (chr4-80202095-CCAG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099403.2(PRDM8):c.649_651delCAG(p.Gln217del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000913 in 1,543,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

PRDM8
NM_001099403.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.793

Variant links:

Genes affected

PRDM8 (HGNC:13993): (PR/SET domain 8) This gene encodes a protein that belongs to a conserved family of histone methyltransferases that predominantly act as negative regulators of transcription. The encoded protein contains an N-terminal Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain and a double zinc-finger domain. Knockout of this gene in mouse results in mistargeting by neurons of the dorsal telencephalon, abnormal itch-like behavior, and impaired differentiation of rod bipolar cells. In humans, the protein has been shown to interact with the phosphatase laforin and the ubiquitin ligase malin, which regulate glycogen construction in the cytoplasm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

PRDM8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM8	NM_001099403.2 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 4 of 4	ENST00000415738.3	NP_001092873.1	Q9NQV8-1A0A024RDC4Q05CA1
PRDM8	NM_020226.4 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 10 of 10		NP_064611.3	Q9NQV8-1A0A024RDC4Q05CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRDM8	ENST00000415738.3 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 4 of 4	1	NM_001099403.2	ENSP00000406998.2	Q9NQV8-1
PRDM8	ENST00000339711.8 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 10 of 10	1		ENSP00000339764.4	Q9NQV8-1
PRDM8	ENST00000515013.5 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 10 of 10	1		ENSP00000425149.1	E9PEH0
PRDM8	ENST00000504452.5 link	c.649_651delCAG	p.Gln217del	conservative_inframe_deletion	Exon 8 of 8	5		ENSP00000423985.1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.0000222

AC:

AN:

135014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000321

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000980

AC:

138

AN:

1408730

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

699960

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

Gnomad4 AMR exome

AF:

0.000191

Gnomad4 ASJ exome

AF:

0.000241

Gnomad4 EAS exome

AF:

0.000184

Gnomad4 SAS exome

AF:

0.000137

Gnomad4 FIN exome

AF:

0.000116

Gnomad4 NFE exome

AF:

0.0000855

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

AF:

0.0000222

AC:

AN:

135118

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

66006

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000114

Gnomad4 NFE

AF:

0.0000322

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0168

Hom.:

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over