10-63465506-G-A

Variant summary

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

The NM_032776.3(JMJD1C):​c.157C>T​(p.Pro53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000895 in 1,451,774 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: 0.0000090 ( 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]
JMJD1C-AS1 (HGNC:28222): (JMJD1C antisense RNA 1)

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=0.31436682).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JMJD1CNM_032776.3 linkc.157C>T p.Pro53Ser missense_variant Exon 1 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.157C>T p.Pro53Ser missense_variant Exon 1 of 26 5 NM_032776.3 ENSP00000382204.2 Q15652-1
JMJD1C-AS1ENST00000609436.1 linkn.278G>A non_coding_transcript_exon_variant Exon 1 of 1 6
JMJD1CENST00000633035.1 linkn.113+56232C>T intron_variant Intron 1 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000264
AC:
6
AN:
226848
Hom.:
0
AF XY:
0.0000322
AC XY:
4
AN XY:
124362
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000149
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000337
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000895
AC:
13
AN:
1451774
Hom.:
0
Cov.:
36
AF XY:
0.0000125
AC XY:
9
AN XY:
721996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000136
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000467
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.0000166
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Early myoclonic encephalopathy Uncertain:1
Dec 19, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 53 of the JMJD1C protein (p.Pro53Ser). This variant is present in population databases (rs748149848, gnomAD 0.02%). 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: 946146). 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
0.12
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.75
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.99
N
REVEL
Benign
0.20
Sift
Benign
0.036
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.32
MutPred
0.39
Gain of phosphorylation at P53 (P = 0.0465);
MVP
0.45
MPC
0.39
ClinPred
0.73
D
GERP RS
4.1
Varity_R
0.083
gMVP
0.37

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