rs1553176454
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022114.4(PRDM16):c.1495C>T(p.Pro499Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,000 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: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
PRDM16
NM_022114.4 missense
NM_022114.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 4.85
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3501618).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.1495C>T | p.Pro499Ser | missense_variant | 9/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.1495C>T | p.Pro499Ser | missense_variant | 9/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.1495C>T | p.Pro499Ser | missense_variant | 9/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458000Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 724766
GnomAD4 exome
AF:
AC:
4
AN:
1458000
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
724766
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Left ventricular noncompaction 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 15, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PRDM16-related disease. This sequence change replaces proline with serine at codon 499 of the PRDM16 protein (p.Pro499Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
0.98, 0.91
.;D;.;P;.
Vest4
MutPred
0.30
.;Gain of phosphorylation at P499 (P = 0.0447);.;Gain of phosphorylation at P499 (P = 0.0447);.;
MVP
MPC
0.70
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at