1-3426240-G-T

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

2

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]

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
PRDM16NM_022114.4 linkc.3284+15G>T intron_variant Intron 14 of 16 ENST00000270722.10 NP_071397.3 Q9HAZ2-1
PRDM16NM_199454.3 linkc.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
PRDM16ENST00000270722.10 linkc.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.:
31
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.:
31
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.:
31
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.

Other links and lift over

dbSNP: rs870171; hg19: chr1-3342804; API