rs374254884
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_022114.4(PRDM16):c.1719G>A(p.Ala573=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,584 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 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 0 hom. )
Consequence
PRDM16
NM_022114.4 synonymous
NM_022114.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.48
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 1-3411916-G-A is Benign according to our data. Variant chr1-3411916-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241423.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-3411916-G-A is described in Lovd as [Benign]. Variant chr1-3411916-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.48 with no splicing effect.
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.1719G>A | p.Ala573= | synonymous_variant | 9/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.1719G>A | p.Ala573= | synonymous_variant | 9/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.1719G>A | p.Ala573= | synonymous_variant | 9/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152130Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000161 AC: 40AN: 248296Hom.: 0 AF XY: 0.000171 AC XY: 23AN XY: 134892
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GnomAD4 exome AF: 0.000309 AC: 451AN: 1461454Hom.: 0 Cov.: 37 AF XY: 0.000296 AC XY: 215AN XY: 727012
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152130Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74312
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Left ventricular noncompaction 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | - - |
Computational scores
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BayesDel_noAF
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at