Genetic Variant PRDM16-DT:n.33_41delGCCGCCGCC (chr1-3069056-AGGCGGCGGC-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000687743.2(PRDM16-DT):n.33_41delGCCGCCGCC 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 0.00497 in 500,596 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0054 ( 2 hom., cov: 29)

Exomes 𝑓: 0.0048 ( 9 hom. )

Consequence

PRDM16-DT
ENST00000687743.2 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

Publications

0 publications found

Variant links:

COSMIC-nc: COSV54598231

Genes affected

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

PRDM16-DT links:

LOC124903827 (HGNC:):

LOC124903827 links:

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

PRDM16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.-203_-195delGGCGGCGGC		upstream_gene_variant		ENST00000270722.10	NP_071397.3	Q9HAZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.-203_-195delGGCGGCGGC		upstream_gene_variant		1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

796

AN:

149146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00607

Gnomad ASJ

AF:

0.00348

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00713

Gnomad OTH

AF:

0.00485

GnomAD4 exome

AF:

0.00481

AC:

1690

AN:

351342

Hom.:

AF XY:

0.00468

AC XY:

910

AN XY:

194370

show subpopulations

African (AFR)

AF:

0.00245

AC:

AN:

6522

American (AMR)

AF:

0.00255

AC:

AN:

12948

Ashkenazi Jewish (ASJ)

AF:

0.00255

AC:

AN:

13728

East Asian (EAS)

AF:

0.000263

AC:

AN:

19044

South Asian (SAS)

AF:

0.00194

AC:

AN:

43374

European-Finnish (FIN)

AF:

0.00988

AC:

297

AN:

30046

Middle Eastern (MID)

AF:

0.00178

AC:

AN:

1682

European-Non Finnish (NFE)

AF:

0.00559

AC:

1146

AN:

204992

Other (OTH)

AF:

0.00374

AC:

AN:

19006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00536

AC:

800

AN:

149254

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

398

AN XY:

72902

show subpopulations

African (AFR)

AF:

0.00225

AC:

AN:

39940

American (AMR)

AF:

0.00606

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00348

AC:

AN:

3452

East Asian (EAS)

AF:

0.000201

AC:

AN:

4970

South Asian (SAS)

AF:

0.00151

AC:

AN:

4650

European-Finnish (FIN)

AF:

0.0104

AC:

107

AN:

10322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00713

AC:

481

AN:

67478

Other (OTH)

AF:

0.00479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00154

Hom.:

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

Publications

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1-3069056-AGGCGGCGGC-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over