rs371540074
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_022114.4(PRDM16):c.714C>A(p.Leu238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
PRDM16
NM_022114.4 synonymous
NM_022114.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0790
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 1-3402828-C-A is Benign according to our data. Variant chr1-3402828-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 227874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3402828-C-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.079 with no splicing effect.
BS2
?
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.714C>A | p.Leu238= | synonymous_variant | 6/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.714C>A | p.Leu238= | synonymous_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.714C>A | p.Leu238= | synonymous_variant | 6/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000644 AC: 16AN: 248586Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135204
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GnomAD4 exome AF: 0.0000541 AC: 79AN: 1460678Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 49AN XY: 726612
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Leu238Leu in exon 6 of PRDM16: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.1% (5/8480) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS). - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2021 | Has not been previously published as pathogenic or benign to our knowledge - |
Left ventricular noncompaction 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at