rs34491125

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032776.3(JMJD1C):c.7200C>G(p.Asp2400Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,314 control chromosomes in the GnomAD database, including 995 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 66 hom., cov: 32)

Exomes 𝑓: 0.031 ( 929 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

22q11.2 deletion syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Illumina
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

JMJD1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031909347).

BP6

Variant 10-63177741-G-C is Benign according to our data. Variant chr10-63177741-G-C is described in ClinVar as Benign. ClinVar VariationId is 460277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.7200C>G	p.Asp2400Glu	missense_variant	Exon 23 of 26	ENST00000399262.7	NP_116165.1	Q15652-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
JMJD1C	ENST00000399262.7 link	c.7200C>G	p.Asp2400Glu	missense_variant	Exon 23 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.6654C>G	p.Asp2218Glu	missense_variant	Exon 22 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.6916C>G		non_coding_transcript_exon_variant	Exon 19 of 22	1
JMJD1C	ENST00000327520.7 link	c.2838C>G	p.Asp946Glu	missense_variant	Exon 12 of 12	2		ENSP00000335929.5	H7BXU7

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3734

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0312

Gnomad OTH

AF:

0.0373

GnomAD2 exomes

AF:

0.0286

AC:

7128

AN:

249382

AF XY:

0.0320

show subpopulations

Gnomad AFR exome

AF:

0.00549

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0858

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00742

Gnomad NFE exome

AF:

0.0287

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0309

AC:

45165

AN:

1461052

Hom.:

929

Cov.:

AF XY:

0.0325

AC XY:

23586

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.00651

AC:

218

AN:

33474

American (AMR)

AF:

0.0169

AC:

754

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0851

AC:

2222

AN:

26120

East Asian (EAS)

AF:

0.000176

AC:

AN:

39684

South Asian (SAS)

AF:

0.0676

AC:

5828

AN:

86210

European-Finnish (FIN)

AF:

0.00757

AC:

404

AN:

53400

Middle Eastern (MID)

AF:

0.0647

AC:

373

AN:

5762

European-Non Finnish (NFE)

AF:

0.0300

AC:

33331

AN:

1111328

Other (OTH)

AF:

0.0336

AC:

2028

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

2120

4240

6360

8480

10600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1282

2564

3846

5128

6410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0245

AC:

3732

AN:

152262

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1824

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00683

AC:

284

AN:

41554

American (AMR)

AF:

0.0309

AC:

472

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

311

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0636

AC:

307

AN:

4830

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0312

AC:

2120

AN:

68006

Other (OTH)

AF:

0.0369

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

177

355

532

710

887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0327

Hom.:

Bravo

AF:

0.0241

TwinsUK

AF:

0.0324

AC:

120

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.00977

AC:

ESP6500EA

AF:

0.0326

AC:

267

ExAC

AF:

0.0284

AC:

3431

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Early myoclonic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;.

Eigen

Benign

-0.062

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

.;N;.

PhyloP100

1.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.31

.;T;T

Sift4G

Benign

0.54

.;T;T

Polyphen

0.48

.;P;.

Vest4

0.11, 0.18

MutPred

0.38

.;Loss of ubiquitination at K2397 (P = 0.0949);.;

MPC

1.3

ClinPred

0.013

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.61

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over