rs761363257
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032776.3(JMJD1C):c.2377C>T(p.Pro793Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
JMJD1C
NM_032776.3 missense
NM_032776.3 missense
Scores
5
5
3
Clinical Significance
Conservation
PhyloP100: 9.22
Genes affected
JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JMJD1C | NM_032776.3 | c.2377C>T | p.Pro793Ser | missense_variant | 8/26 | ENST00000399262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JMJD1C | ENST00000399262.7 | c.2377C>T | p.Pro793Ser | missense_variant | 8/26 | 5 | NM_032776.3 | ||
JMJD1C | ENST00000542921.5 | c.1831C>T | p.Pro611Ser | missense_variant | 7/25 | 1 | P1 | ||
JMJD1C | ENST00000402544.5 | n.2349C>T | non_coding_transcript_exon_variant | 5/22 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249054Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135122
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461758Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727176
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early myoclonic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 2017 | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs761363257, ExAC 0.009%) but has not been reported in the literature in individuals with a JMJD1C-related disease. This sequence change replaces proline with serine at codon 793 of the JMJD1C protein (p.Pro793Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D;.
Vest4
0.85, 0.76
MutPred
0.29
.;Gain of glycosylation at P793 (P = 0.0181);.;
MVP
0.72
MPC
0.40
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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