rs199614349
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_022114.4(PRDM16):c.201G>A(p.Pro67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,611,576 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 14 hom. )
Consequence
PRDM16
NM_022114.4 synonymous
NM_022114.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.823
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 1-3186288-G-A is Benign according to our data. Variant chr1-3186288-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3186288-G-A is described in Lovd as [Benign]. Variant chr1-3186288-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.823 with no splicing effect.
BS2
?
High AC in GnomAd4 at 246 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.201G>A | p.Pro67= | synonymous_variant | 2/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.201G>A | p.Pro67= | synonymous_variant | 2/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.201G>A | p.Pro67= | synonymous_variant | 2/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00162 AC: 246AN: 152168Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00225 AC: 552AN: 245588Hom.: 4 AF XY: 0.00244 AC XY: 326AN XY: 133878
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GnomAD4 exome AF: 0.00173 AC: 2521AN: 1459290Hom.: 14 Cov.: 31 AF XY: 0.00179 AC XY: 1302AN XY: 725834
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GnomAD4 genome ? AF: 0.00162 AC: 246AN: 152286Hom.: 1 Cov.: 33 AF XY: 0.00169 AC XY: 126AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | p.Pro67Pro in exon 2 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 0.3% (212/64514) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs199614349). - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 17, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2017 | 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. - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Left ventricular noncompaction 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at