rs747277382
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_022114.4(PRDM16):c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,611,222 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
PRDM16
NM_022114.4 3_prime_UTR
NM_022114.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.843
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS2
High AC in GnomAdExome4 at 90 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.*14C>T | 3_prime_UTR_variant | 17/17 | ENST00000270722.10 | ||
PRDM16 | NM_199454.3 | c.*14C>T | 3_prime_UTR_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.*14C>T | 3_prime_UTR_variant | 17/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 244968Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133470
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GnomAD4 exome AF: 0.0000617 AC: 90AN: 1458990Hom.: 0 Cov.: 32 AF XY: 0.0000606 AC XY: 44AN XY: 725804
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 23, 2017 | The c.*14C>T variant in PRDM16 has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/64412 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs7 47277382). This variant is located in the 3' UTR and its impact is unclear. In s ummary, the clinical significance of the c.*14C>T variant is uncertain. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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