1-3069056-AGGCGGCGGCGGCGGC-AGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr1-3069056-A-AGGCGGCGGCGGC
• rs534904951
• ENST00000687743.2:n.30_41dupGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000687743.2(PRDM16-DT):​n.30_41dupGCCGCCGCCGCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 351,456 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: 29)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PRDM16-DT ENST00000687743.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 0 publications found

Genes affected

PRDM16-DT (HGNC:48664): (PRDM16 divergent transcript)

LOC124903827 (HGNC:):

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM16 Gene-Disease associations (from GenCC):

• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.-204_-203insGGCGGCGGCGGC		upstream_gene_variant		ENST00000270722.10	NP_071397.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.-204_-203insGGCGGCGGCGGC		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000285 AC: 1 AN: 351456 Hom.: 0 AF XY: 0.00000514 AC XY: 1 AN XY: 194448

African (AFR) AF: 0.00 AC: 0 AN: 6524

American (AMR) AF: 0.00 AC: 0 AN: 12950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13728

East Asian (EAS) AF: 0.00 AC: 0 AN: 19044

South Asian (SAS) AF: 0.00 AC: 0 AN: 43390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1682

European-Non Finnish (NFE) AF: 0.00000488 AC: 1 AN: 205068

Other (OTH) AF: 0.00 AC: 0 AN: 19012

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs534904951; hg19: chr1-2985620;