rs758774731
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_022114.4(PRDM16):c.3369_3371dup(p.Asp1124dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000299 in 1,613,700 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E1121E) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 3 hom. )
Consequence
PRDM16
NM_022114.4 inframe_insertion
NM_022114.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.62
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 -12 ACMG points.
BP6
?
Variant 1-3430950-G-GGAC is Benign according to our data. Variant chr1-3430950-G-GGAC is described in ClinVar as [Likely_benign]. Clinvar id is 413868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 53 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.3369_3371dup | p.Asp1124dup | inframe_insertion | 15/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.3369_3371dup | p.Asp1124dup | inframe_insertion | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.3369_3371dup | p.Asp1124dup | inframe_insertion | 15/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152234Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000514 AC: 127AN: 247138Hom.: 0 AF XY: 0.000469 AC XY: 63AN XY: 134192
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GnomAD4 exome AF: 0.000294 AC: 429AN: 1461348Hom.: 3 Cov.: 32 AF XY: 0.000316 AC XY: 230AN XY: 726926
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GnomAD4 genome ? AF: 0.000348 AC: 53AN: 152352Hom.: 1 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74504
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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 | Nov 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 | Jun 28, 2017 | p.Asp1125dup in exon 15 of PRDM16: This variant is not expected to have clinical significance as it is present in 1.077% of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs7 58774731). This variant represents an inframe duplication in a repetitive region containing several aspartic acids (Asp). - |
Left ventricular noncompaction 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at