1-3426240-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022114.4(PRDM16):c.3284+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,607,588 control chromosomes in the GnomAD database, including 70,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8231 hom., cov: 31)

Exomes 𝑓: 0.29 ( 61834 hom. )

Consequence

PRDM16
NM_022114.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.15

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-3426240-G-T is Benign according to our data. Variant chr1-3426240-G-T is described in ClinVar as [Benign]. Clinvar id is 227035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4 link	c.3284+15G>T		intron_variant	Intron 14 of 16	ENST00000270722.10	NP_071397.3	Q9HAZ2-1
PRDM16	NM_199454.3 link	c.3284+15G>T		intron_variant	Intron 14 of 16		NP_955533.2	Q9HAZ2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10 link	c.3284+15G>T		intron_variant	Intron 14 of 16	1	NM_022114.4	ENSP00000270722.5		Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48586

AN:

151736

Hom.:

8215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.295

AC:

72759

AN:

246792

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.288

AC:

419424

AN:

1455734

Hom.:

61834

Cov.:

AF XY:

0.287

AC XY:

207530

AN XY:

723644

show subpopulations

African (AFR)

AF:

0.419

AC:

13967

AN:

33310

American (AMR)

AF:

0.285

AC:

12679

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

7112

AN:

25930

East Asian (EAS)

AF:

0.433

AC:

17140

AN:

39602

South Asian (SAS)

AF:

0.277

AC:

23774

AN:

85912

European-Finnish (FIN)

AF:

0.227

AC:

12090

AN:

53162

Middle Eastern (MID)

AF:

0.264

AC:

1518

AN:

5746

European-Non Finnish (NFE)

AF:

0.283

AC:

312882

AN:

1107454

Other (OTH)

AF:

0.304

AC:

18262

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

14022

28045

42067

56090

70112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10762

21524

32286

43048

53810

<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:

0.320

AC:

48655

AN:

151854

Hom.:

8231

Cov.:

AF XY:

0.317

AC XY:

23505

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.420

AC:

17394

AN:

41420

American (AMR)

AF:

0.300

AC:

4586

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

898

AN:

3464

East Asian (EAS)

AF:

0.483

AC:

2469

AN:

5114

South Asian (SAS)

AF:

0.277

AC:

1330

AN:

4810

European-Finnish (FIN)

AF:

0.230

AC:

2428

AN:

10548

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18611

AN:

67914

Other (OTH)

AF:

0.326

AC:

686

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1647

3295

4942

6590

8237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.282

Hom.:

13895

Bravo

AF:

0.331

Asia WGS

AF:

0.395

AC:

1371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

3284+15G>T in intron 14 of PRDM16: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 40.6% (1578/3884) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs870171). -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 23, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Left ventricular noncompaction 8

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

(source)

DANN

Benign

0.20

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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