chr1-3069056-AGGCGGC-A

Variant names:

• chr1-3069056-AGGCGGC-A
• rs534904951
• ENST00000687743.2:n.36_41delGCCGCC

Variant summary

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

The ENST00000687743.2(PRDM16-DT):​n.36_41delGCCGCC 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 0.0004 in 500,604 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 0.00051 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: PRDM16-DT ENST00000687743.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• 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_-198delGGCGGC		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_-198delGGCGGC		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.000503 AC: 75 AN: 149166 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000594

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00100

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000459

Gnomad OTH AF: 0.000970

GnomAD4 exome AF: 0.000353 AC: 124 AN: 351330 Hom.: 0 AF XY: 0.000345 AC XY: 67 AN XY: 194378

African (AFR) AF: 0.000614 AC: 4 AN: 6516

American (AMR) AF: 0.0000772 AC: 1 AN: 12948

Ashkenazi Jewish (ASJ) AF: 0.0000729 AC: 1 AN: 13722

East Asian (EAS) AF: 0.000210 AC: 4 AN: 19038

South Asian (SAS) AF: 0.000277 AC: 12 AN: 43372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30052

Middle Eastern (MID) AF: 0.00238 AC: 4 AN: 1682

European-Non Finnish (NFE) AF: 0.000449 AC: 92 AN: 204990

Other (OTH) AF: 0.000316 AC: 6 AN: 19010

GnomAD4 genome AF: 0.000509 AC: 76 AN: 149274 Hom.: 0 Cov.: 29 AF XY: 0.000521 AC XY: 38 AN XY: 72916

African (AFR) AF: 0.000726 AC: 29 AN: 39946

American (AMR) AF: 0.000593 AC: 9 AN: 15174

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

East Asian (EAS) AF: 0.00101 AC: 5 AN: 4970

South Asian (SAS) AF: 0.00 AC: 0 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: 0.000459 AC: 31 AN: 67484

Other (OTH) AF: 0.000959 AC: 2 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		1.8

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;