10-63465485-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032776.3(JMJD1C):​c.168+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,592,154 control chromosomes in the GnomAD database, including 785,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70903 hom., cov: 34)
Exomes 𝑓: 1.0 ( 714554 hom. )

Consequence

JMJD1C
NM_032776.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 10-63465485-A-G is Benign according to our data. Variant chr10-63465485-A-G is described in ClinVar as [Benign]. Clinvar id is 1164927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
JMJD1CNM_032776.3 linkuse as main transcriptc.168+10T>C intron_variant ENST00000399262.7 NP_116165.1
JMJD1C-AS1NR_027182.1 linkuse as main transcriptn.257A>G non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
JMJD1CENST00000399262.7 linkuse as main transcriptc.168+10T>C intron_variant 5 NM_032776.3 ENSP00000382204 Q15652-1
JMJD1C-AS1ENST00000609436.1 linkuse as main transcriptn.257A>G non_coding_transcript_exon_variant 1/1
JMJD1CENST00000633035.1 linkuse as main transcriptn.113+56253T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.963
AC:
146628
AN:
152208
Hom.:
70852
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.874
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.985
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.987
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.968
GnomAD3 exomes
AF:
0.990
AC:
216064
AN:
218256
Hom.:
107054
AF XY:
0.992
AC XY:
118918
AN XY:
119894
show subpopulations
Gnomad AFR exome
AF:
0.862
Gnomad AMR exome
AF:
0.993
Gnomad ASJ exome
AF:
0.999
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.999
Gnomad OTH exome
AF:
0.995
GnomAD4 exome
AF:
0.996
AC:
1434146
AN:
1439828
Hom.:
714554
Cov.:
41
AF XY:
0.997
AC XY:
712348
AN XY:
714838
show subpopulations
Gnomad4 AFR exome
AF:
0.866
Gnomad4 AMR exome
AF:
0.993
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.991
GnomAD4 genome
AF:
0.963
AC:
146738
AN:
152326
Hom.:
70903
Cov.:
34
AF XY:
0.964
AC XY:
71816
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.874
Gnomad4 AMR
AF:
0.985
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.999
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.999
Gnomad4 OTH
AF:
0.969
Alfa
AF:
0.994
Hom.:
56945
Bravo
AF:
0.958
Asia WGS
AF:
0.992
AC:
3450
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 06, 2021- -
Early myoclonic encephalopathy Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
12
DANN
Benign
0.70

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: rs10761770; hg19: chr10-65225245; API