rs199853370

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_022114.4(PRDM16):​c.3102C>T​(p.Asn1034Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,524 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 11 hom. )

Consequence

PRDM16
NM_022114.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.06
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 -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 1-3425743-C-T is Benign according to our data. Variant chr1-3425743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3425743-C-T is described in Lovd as [Benign]. Variant chr1-3425743-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BS2
High AC in GnomAd4 at 228 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRDM16NM_022114.4 linkuse as main transcriptc.3102C>T p.Asn1034Asn synonymous_variant 13/17 ENST00000270722.10 NP_071397.3 Q9HAZ2-1
PRDM16NM_199454.3 linkuse as main transcriptc.3102C>T p.Asn1034Asn synonymous_variant 13/17 NP_955533.2 Q9HAZ2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRDM16ENST00000270722.10 linkuse as main transcriptc.3102C>T p.Asn1034Asn synonymous_variant 13/171 NM_022114.4 ENSP00000270722.5 Q9HAZ2-1

Frequencies

GnomAD3 genomes
AF:
0.00151
AC:
229
AN:
152154
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00443
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00184
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00181
AC:
451
AN:
248886
Hom.:
2
AF XY:
0.00203
AC XY:
274
AN XY:
135158
show subpopulations
Gnomad AFR exome
AF:
0.0000647
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00173
Gnomad FIN exome
AF:
0.00627
Gnomad NFE exome
AF:
0.00176
Gnomad OTH exome
AF:
0.00331
GnomAD4 exome
AF:
0.00213
AC:
3117
AN:
1461252
Hom.:
11
Cov.:
32
AF XY:
0.00215
AC XY:
1566
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.00119
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00168
Gnomad4 FIN exome
AF:
0.00661
Gnomad4 NFE exome
AF:
0.00214
Gnomad4 OTH exome
AF:
0.00268
GnomAD4 genome
AF:
0.00150
AC:
228
AN:
152272
Hom.:
1
Cov.:
32
AF XY:
0.00145
AC XY:
108
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00443
Gnomad4 NFE
AF:
0.00184
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00151
Hom.:
0
Bravo
AF:
0.00159
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00245
EpiControl
AF:
0.00284

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:6
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2024PRDM16: BP4, BP7 -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 03, 2023- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 05, 2019- -
not specified Benign:2
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Left ventricular noncompaction 8 Benign:2
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMay 02, 2022- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
PRDM16-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 20, 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
-0.41
CADD
Benign
3.4
DANN
Benign
0.81

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: rs199853370; hg19: chr1-3342307; COSMIC: COSV54587101; API