10-63168063-C-G

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.7605G>C(p.Glu2535Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,584,334 control chromosomes in the GnomAD database, including 173,701 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 0.43 ( 14532 hom., cov: 32)

Exomes 𝑓: 0.47 ( 159169 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00500

Publications

79 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=2.9492378E-4).

BP6

Variant 10-63168063-C-G is Benign according to our data. Variant chr10-63168063-C-G is described in ClinVar as Benign. ClinVar VariationId is 1167960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.7605G>C	p.Glu2535Asp	missense_variant	Exon 26 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
JMJD1C	ENST00000399262.7 link	c.7605G>C	p.Glu2535Asp	missense_variant	Exon 26 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5 link	c.7059G>C	p.Glu2353Asp	missense_variant	Exon 25 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5 link	n.7296G>C		non_coding_transcript_exon_variant	Exon 22 of 22	1
JMJD1C	ENST00000467356.5 link	n.463G>C		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64991

AN:

151814

Hom.:

14546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.427

GnomAD2 exomes

AF:

0.438

AC:

108928

AN:

248440

AF XY:

0.452

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.467

AC:

668979

AN:

1432402

Hom.:

159169

Cov.:

AF XY:

0.472

AC XY:

337084

AN XY:

714480

show subpopulations

African (AFR)

AF:

0.322

AC:

10588

AN:

32908

American (AMR)

AF:

0.260

AC:

11604

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

14814

AN:

25906

East Asian (EAS)

AF:

0.418

AC:

16500

AN:

39500

South Asian (SAS)

AF:

0.533

AC:

45572

AN:

85508

European-Finnish (FIN)

AF:

0.478

AC:

25201

AN:

52718

Middle Eastern (MID)

AF:

0.438

AC:

2508

AN:

5720

European-Non Finnish (NFE)

AF:

0.474

AC:

515127

AN:

1086142

Other (OTH)

AF:

0.456

AC:

27065

AN:

59410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14846

29692

44538

59384

74230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14902

29804

44706

59608

74510

<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:

0.428

AC:

64963

AN:

151932

Hom.:

14532

Cov.:

AF XY:

0.428

AC XY:

31758

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.326

AC:

13525

AN:

41450

American (AMR)

AF:

0.344

AC:

5253

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2038

AN:

3468

East Asian (EAS)

AF:

0.354

AC:

1829

AN:

5160

South Asian (SAS)

AF:

0.532

AC:

2566

AN:

4824

European-Finnish (FIN)

AF:

0.476

AC:

5017

AN:

10548

Middle Eastern (MID)

AF:

0.425

AC:

124

AN:

292

European-Non Finnish (NFE)

AF:

0.488

AC:

33140

AN:

67914

Other (OTH)

AF:

0.425

AC:

894

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1858

3716

5575

7433

9291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.479

Hom.:

13748

Bravo

AF:

0.405

TwinsUK

AF:

0.486

AC:

1803

ALSPAC

AF:

0.475

AC:

1831

ESP6500AA

AF:

0.340

AC:

1271

ESP6500EA

AF:

0.478

AC:

3919

ExAC

AF:

0.445

AC:

53808

Asia WGS

AF:

0.418

AC:

1452

AN:

3476

EpiCase

AF:

0.488

EpiControl

AF:

0.480

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

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.00029

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

.;L;.

PhyloP100

0.0050

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.38

.;N;N

REVEL

Benign

0.090

Sift

Benign

0.17

.;T;T

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

0.35

.;B;.

Vest4

0.060, 0.16

MutPred

0.095

.;Loss of loop (P = 0.1258);.;

MPC

0.99

ClinPred

0.013

GERP RS

3.6

Varity_R

0.054

gMVP

0.16

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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