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rs34825545

chr10-63193074-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_032776.3(JMJD1C):c.5940G>A(p.Pro1980=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,614,034 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0058 ( 52 hom. )

Consequence

JMJD1C
NM_032776.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01
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 Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-63193074-C-T is Benign according to our data. Variant chr10-63193074-C-T is described in ClinVar as [Benign]. Clinvar id is 460263.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.01 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00464 (707/152228) while in subpopulation SAS AF= 0.0188 (91/4830). AF 95% confidence interval is 0.0157. There are 7 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 709 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JMJD1CNM_032776.3 linkuse as main transcriptc.5940G>A p.Pro1980= synonymous_variant 16/26 ENST00000399262.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JMJD1CENST00000399262.7 linkuse as main transcriptc.5940G>A p.Pro1980= synonymous_variant 16/265 NM_032776.3 Q15652-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00466
AC:
709
AN:
152110
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00145
Gnomad AMI
AF:
0.0592
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0192
Gnomad FIN
AF:
0.00917
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00491
Gnomad OTH
AF:
0.00527
GnomAD3 exomes
AF:
0.00616
AC:
1536
AN:
249434
Hom.:
11
AF XY:
0.00679
AC XY:
919
AN XY:
135322
show subpopulations
Gnomad AFR exome
AF:
0.00110
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00447
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0202
Gnomad FIN exome
AF:
0.00914
Gnomad NFE exome
AF:
0.00526
Gnomad OTH exome
AF:
0.00462
GnomAD4 exome
AF:
0.00577
AC:
8431
AN:
1461806
Hom.:
52
Cov.:
31
AF XY:
0.00616
AC XY:
4480
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.000986
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00429
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0194
Gnomad4 FIN exome
AF:
0.00850
Gnomad4 NFE exome
AF:
0.00522
Gnomad4 OTH exome
AF:
0.00445
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00464
AC:
707
AN:
152228
Hom.:
7
Cov.:
32
AF XY:
0.00459
AC XY:
342
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.00144
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0188
Gnomad4 FIN
AF:
0.00917
Gnomad4 NFE
AF:
0.00491
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00500
Hom.:
4
Bravo
AF:
0.00374
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.00507
EpiControl
AF:
0.00545

ClinVar

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

Submissions by phenotype

Early myoclonic encephalopathy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
12
Dann
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs34825545; hg19: chr10-64952834; API