1-3426240-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr1-3426240-G-T is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.295

AC:

72759

AN:

246792

Hom.:

11317

AF XY:

0.291

AC XY:

38968

AN XY:

133982

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 SAS exome

AF:

0.276

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

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.320

AC:

48655

AN:

151854

Hom.:

8231

Cov.:

AF XY:

0.317

AC XY:

23505

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.273

Hom.:

8167

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

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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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). -

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. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Left ventricular noncompaction 8

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

DANN

Benign

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over