1-3069056-AGGCGGCGGCGGC-A

Variant names:

• chr1-3069056-AGGCGGCGGCGGC-A
• rs534904951
• ENST00000687743.2:n.30_41delGCCGCCGCCGCC

Variant summary

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

The ENST00000687743.2(PRDM16-DT):​n.30_41delGCCGCCGCCGCC 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 0.000128 in 500,706 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 DEL_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: 𝑓 0.00015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PRDM16-DT ENST00000687743.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• 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.-203_-192delGGCGGCGGCGGC		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.-203_-192delGGCGGCGGCGGC		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 23 AN: 149162 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000803

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000593

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 41 AN: 351436 Hom.: 0 AF XY: 0.000139 AC XY: 27 AN XY: 194436

African (AFR) AF: 0.000153 AC: 1 AN: 6524

American (AMR) AF: 0.000232 AC: 3 AN: 12950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13726

East Asian (EAS) AF: 0.000210 AC: 4 AN: 19044

South Asian (SAS) AF: 0.000184 AC: 8 AN: 43388

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

Middle Eastern (MID) AF: 0.000595 AC: 1 AN: 1682

European-Non Finnish (NFE) AF: 0.000102 AC: 21 AN: 205056

Other (OTH) AF: 0.000158 AC: 3 AN: 19008

GnomAD4 genome AF: 0.000154 AC: 23 AN: 149270 Hom.: 0 Cov.: 29 AF XY: 0.000151 AC XY: 11 AN XY: 72914

African (AFR) AF: 0.000325 AC: 13 AN: 39944

American (AMR) AF: 0.0000659 AC: 1 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.000805 AC: 4 AN: 4970

South Asian (SAS) AF: 0.000215 AC: 1 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000593 AC: 4 AN: 67484

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

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;