chr4-80202310-T-TCAGCAGCGGTAG

Variant names:

• chr4-80202310-T-TCAGCAGCGGTAG
• rs1455395711
• NM_001099403.2:c.850_861dupAGCAGCGGTAGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001099403.2(PRDM8):​c.850_861dupAGCAGCGGTAGC​(p.Ser284_Ser287dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,457,286 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PRDM8 NM_001099403.2 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• early-onset Lafora body disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001099403.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099403.2. 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
	PRDM8	NM_001099403.2	MANE Select	c.850_861dupAGCAGCGGTAGC	p.Ser284_Ser287dup	conservative_inframe_insertion	Exon 4 of 4	NP_001092873.1	Q9NQV8-1
	PRDM8	NM_020226.4		c.850_861dupAGCAGCGGTAGC	p.Ser284_Ser287dup	conservative_inframe_insertion	Exon 10 of 10	NP_064611.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM8	ENST00000415738.3	TSL:1 MANE Select	c.850_861dupAGCAGCGGTAGC	p.Ser284_Ser287dup	conservative_inframe_insertion	Exon 4 of 4	ENSP00000406998.2	Q9NQV8-1
	PRDM8	ENST00000339711.8	TSL:1	c.850_861dupAGCAGCGGTAGC	p.Ser284_Ser287dup	conservative_inframe_insertion	Exon 10 of 10	ENSP00000339764.4	Q9NQV8-1
	PRDM8	ENST00000515013.5	TSL:1	c.850_861dupAGCAGCGGTAGC	p.Ser284_Ser287dup	conservative_inframe_insertion	Exon 10 of 10	ENSP00000425149.1	E9PEH0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1457286 Hom.: 0 Cov.: 37 AF XY: 0.00000414 AC XY: 3 AN XY: 725030

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000991 AC: 11 AN: 1109930

Other (OTH) AF: 0.00 AC: 0 AN: 60162

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.090

Splicing

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

Other links and lift over

dbSNP: rs1455395711; hg19: chr4-81123464;