rs748593482

chr4-80202095-CCAG-Cchr4-80202095-CCAG-CCAGCAGchr4-80202095-CCAG-CCAGCAGCAG

Variant summary

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

The NM_001099403.2(PRDM8):c.649_651del(p.Gln217del) variant causes a 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 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793

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]

ACMG classification

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/exons	MANE	UniProt
PRDM8	NM_001099403.2	c.649_651del	p.Gln217del	inframe_deletion	4/4	ENST00000415738.3
PRDM8	NM_020226.4	c.649_651del	p.Gln217del	inframe_deletion	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM8	ENST00000415738.3	c.649_651del	p.Gln217del	inframe_deletion	4/4	1	NM_001099403.2	P1
PRDM8	ENST00000339711.8	c.649_651del	p.Gln217del	inframe_deletion	10/10	1		P1
PRDM8	ENST00000515013.5	c.649_651del	p.Gln217del	inframe_deletion	10/10	1
PRDM8	ENST00000504452.5	c.649_651del	p.Gln217del	inframe_deletion	8/8	5		P1

Frequencies

GnomAD3 genomes AF: 0.0000222 AC: 3 AN: 135014 Hom.: 0 Cov.: 31

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.: 0 AF XY: 0.000114 AC XY: 80 AN XY: 699960

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: 3 AN: 135118 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 2 AN XY: 66006

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.: 0

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs748593482; hg19: chr4-81123249;