10-63465506-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032776.3(JMJD1C):ā€‹c.157C>Gā€‹(p.Pro53Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000561 in 1,604,014 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29974174).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
JMJD1CNM_032776.3 linkuse as main transcriptc.157C>G p.Pro53Ala missense_variant 1/26 ENST00000399262.7 NP_116165.1 Q15652-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
JMJD1CENST00000399262.7 linkuse as main transcriptc.157C>G p.Pro53Ala missense_variant 1/265 NM_032776.3 ENSP00000382204.2 Q15652-1
JMJD1C-AS1ENST00000609436.1 linkuse as main transcriptn.278G>C non_coding_transcript_exon_variant 1/16
JMJD1CENST00000633035.1 linkuse as main transcriptn.113+56232C>G intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000176
AC:
4
AN:
226848
Hom.:
0
AF XY:
0.00000804
AC XY:
1
AN XY:
124362
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000893
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000177
GnomAD4 exome
AF:
0.00000413
AC:
6
AN:
1451774
Hom.:
0
Cov.:
36
AF XY:
0.00000139
AC XY:
1
AN XY:
721996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000904
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000113
ExAC
AF:
0.0000166
AC:
2

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 53 of the JMJD1C protein (p.Pro53Ala). This variant is present in population databases (rs748149848, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with JMJD1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 842120). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.73
T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.16
Sift
Benign
0.15
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.35
MutPred
0.42
Gain of MoRF binding (P = 0.0604);
MVP
0.46
MPC
0.24
ClinPred
0.87
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.051
gMVP
0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748149848; hg19: chr10-65225266; API