rs3819970

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022114.4(PRDM16):​c.2673G>A​(p.Pro891Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,613,104 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 32 hom., cov: 33)
Exomes 𝑓: 0.0041 ( 274 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.21
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 1-3414629-G-A is Benign according to our data. Variant chr1-3414629-G-A is described in ClinVar as [Benign]. Clinvar id is 227031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3414629-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.2 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRDM16NM_022114.4 linkuse as main transcriptc.2673G>A p.Pro891Pro synonymous_variant 10/17 ENST00000270722.10 NP_071397.3 Q9HAZ2-1
PRDM16NM_199454.3 linkuse as main transcriptc.2673G>A p.Pro891Pro synonymous_variant 10/17 NP_955533.2 Q9HAZ2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRDM16ENST00000270722.10 linkuse as main transcriptc.2673G>A p.Pro891Pro synonymous_variant 10/171 NM_022114.4 ENSP00000270722.5 Q9HAZ2-1

Frequencies

GnomAD3 genomes
AF:
0.00677
AC:
1030
AN:
152120
Hom.:
32
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00198
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0512
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.0253
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.0164
AC:
4015
AN:
244800
Hom.:
211
AF XY:
0.0127
AC XY:
1690
AN XY:
133498
show subpopulations
Gnomad AFR exome
AF:
0.00198
Gnomad AMR exome
AF:
0.0960
Gnomad ASJ exome
AF:
0.00191
Gnomad EAS exome
AF:
0.0333
Gnomad SAS exome
AF:
0.000197
Gnomad FIN exome
AF:
0.0000468
Gnomad NFE exome
AF:
0.0000456
Gnomad OTH exome
AF:
0.0105
GnomAD4 exome
AF:
0.00409
AC:
5978
AN:
1460866
Hom.:
274
Cov.:
31
AF XY:
0.00364
AC XY:
2643
AN XY:
726778
show subpopulations
Gnomad4 AFR exome
AF:
0.00131
Gnomad4 AMR exome
AF:
0.0927
Gnomad4 ASJ exome
AF:
0.00153
Gnomad4 EAS exome
AF:
0.0355
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000567
Gnomad4 OTH exome
AF:
0.00442
GnomAD4 genome
AF:
0.00678
AC:
1032
AN:
152238
Hom.:
32
Cov.:
33
AF XY:
0.00727
AC XY:
541
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.00197
Gnomad4 AMR
AF:
0.0513
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.0253
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00183
Hom.:
2
Bravo
AF:
0.0114
Asia WGS
AF:
0.0120
AC:
42
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:6
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineNov 24, 2014Pro891Pro in exon 10 of PRDM16: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 12.9% (17/132) of Mexican chromosomes from a broad population by the 1000 Genomes Project (http:// www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs3819970). -
Benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpMay 28, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 11, 2016This 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. -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Left ventricular noncompaction 8 Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 28, 2024- -
Benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsSep 09, 2021- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
PRDM16-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 10, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.14
DANN
Benign
0.62

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: rs3819970; hg19: chr1-3331193; COSMIC: COSV104542603; API