rs538723120
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_022114.4(PRDM16):c.2940-15G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,612,932 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: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
PRDM16
NM_022114.4 splice_polypyrimidine_tract, intron
NM_022114.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.539
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 -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 1-3425566-G-A is Benign according to our data. Variant chr1-3425566-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 229167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-3425566-G-A is described in Lovd as [Benign].
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.2940-15G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000270722.10 | |||
PRDM16 | NM_199454.3 | c.2940-15G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.2940-15G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000185 AC: 46AN: 248130Hom.: 0 AF XY: 0.000252 AC XY: 34AN XY: 134720
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GnomAD4 exome AF: 0.0000876 AC: 128AN: 1460724Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 96AN XY: 726690
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74424
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 08, 2019 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Left ventricular noncompaction 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | - - |
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