rs200016210

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032776.3(JMJD1C):​c.1120G>T​(p.Asp374Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

4
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.48
Variant links:
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 rank MANE Protein UniProt
JMJD1CNM_032776.3 linkc.1120G>T p.Asp374Tyr missense_variant Exon 8 of 26 ENST00000399262.7 NP_116165.1 Q15652-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JMJD1CENST00000399262.7 linkc.1120G>T p.Asp374Tyr missense_variant Exon 8 of 26 5 NM_032776.3 ENSP00000382204.2 Q15652-1
JMJD1CENST00000542921.5 linkc.574G>T p.Asp192Tyr missense_variant Exon 7 of 25 1 ENSP00000444682.1 Q15652-3
JMJD1CENST00000402544.5 linkn.1092G>T non_coding_transcript_exon_variant Exon 5 of 22 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1455926
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
723948
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
.;T;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.51
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
.;M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.8
.;D;D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
.;D;D
Sift4G
Uncertain
0.0040
.;D;D
Polyphen
1.0
.;D;.
Vest4
0.81, 0.73
MutPred
0.17
.;Gain of phosphorylation at D374 (P = 0.0187);.;
MVP
0.36
MPC
0.44
ClinPred
0.99
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.68
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-64974807; API