1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022114.4(PRDM16):c.884+39_884+69delACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,590,522 control chromosomes in the GnomAD database, including 280 homozygotes. 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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 147 hom. )

Consequence

PRDM16
NM_022114.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.87

Publications

0 publications found

Variant links:

Genes affected

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G is Benign according to our data. Variant chr1-3403006-GCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA-G is described in ClinVar as Benign. ClinVar VariationId is 406244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.884+39_884+69delACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT		intron_variant	Intron 6 of 16	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3 link	c.884+39_884+69delACCCTCCTCTGAGTCTTCCTCCCCTTCCCGT		intron_variant	Intron 6 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.884+9_884+39delCCCTCCTCTGAGTCTTCCTCCCCTTCCCGTA		intron_variant	Intron 6 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3682

AN:

144354

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00349

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000654

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.000946

Gnomad OTH

AF:

0.0194

GnomAD2 exomes

AF:

0.00508

AC:

1230

AN:

242072

AF XY:

0.00394

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000915

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00296

AC:

4286

AN:

1446052

Hom.:

147

AF XY:

0.00266

AC XY:

1912

AN XY:

718496

show subpopulations

African (AFR)

AF:

0.0834

AC:

2660

AN:

31900

American (AMR)

AF:

0.00713

AC:

317

AN:

44466

Ashkenazi Jewish (ASJ)

AF:

0.00269

AC:

AN:

26008

East Asian (EAS)

AF:

0.00

AC:

AN:

39374

South Asian (SAS)

AF:

0.000503

AC:

AN:

85534

European-Finnish (FIN)

AF:

0.000193

AC:

AN:

51742

Middle Eastern (MID)

AF:

0.00949

AC:

AN:

4638

European-Non Finnish (NFE)

AF:

0.000669

AC:

738

AN:

1102896

Other (OTH)

AF:

0.00679

AC:

404

AN:

59494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

194

388

583

777

971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0255

AC:

3691

AN:

144470

Hom.:

133

Cov.:

AF XY:

0.0249

AC XY:

1763

AN XY:

70708

show subpopulations

African (AFR)

AF:

0.0927

AC:

3372

AN:

36362

American (AMR)

AF:

0.0133

AC:

197

AN:

14858

Ashkenazi Jewish (ASJ)

AF:

0.00349

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.000654

AC:

AN:

4586

European-Finnish (FIN)

AF:

0.000194

AC:

AN:

10328

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000946

AC:

AN:

66578

Other (OTH)

AF:

0.0192

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0113

Hom.:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 05, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.884+39_884+69del in intron 6 of PRDM16: This variant is not expected to have c linical significance because it has been identified at a frequency of 22.4% (192 18/85718 chromosomes) across all populations by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148238606). -

Left ventricular noncompaction 8

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over