rs777464880
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The ENST00000270722.10(PRDM16):āc.657A>Cā(p.Thr219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,441,842 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
PRDM16
ENST00000270722.10 synonymous
ENST00000270722.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.387
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
Variant 1-3396574-A-C is Benign according to our data. Variant chr1-3396574-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 227872.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.657A>C | p.Thr219= | synonymous_variant | 5/17 | ENST00000270722.10 | NP_071397.3 | |
PRDM16 | NM_199454.3 | c.657A>C | p.Thr219= | synonymous_variant | 5/17 | NP_955533.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.657A>C | p.Thr219= | synonymous_variant | 5/17 | 1 | NM_022114.4 | ENSP00000270722 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000136 AC: 3AN: 221332Hom.: 0 AF XY: 0.0000250 AC XY: 3AN XY: 120064
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GnomAD4 exome AF: 0.00000624 AC: 9AN: 1441842Hom.: 0 Cov.: 28 AF XY: 0.00000558 AC XY: 4AN XY: 716264
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 01, 2015 | p.Thr219Thr in exon 5 of PRDM16: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has also been identified in 3/29286 Fin nish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org). - |
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