10-63214620-G-C

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.1547C>G(p.Thr516Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,613,868 control chromosomes in the GnomAD database, including 2,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T516A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.035 ( 286 hom., cov: 32)

Exomes 𝑓: 0.035 ( 2056 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.31

Publications

14 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=0.0019951463).

BP6

Variant 10-63214620-G-C is Benign according to our data. Variant chr10-63214620-G-C is described in ClinVar as Benign. ClinVar VariationId is 460220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.1547C>G	p.Thr516Ser	missense_variant	Exon 8 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.1547C>G	p.Thr516Ser	missense_variant	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.1001C>G	p.Thr334Ser	missense_variant	Exon 7 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.1519C>G		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5324

AN:

152118

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00917

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0902

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0268

GnomAD2 exomes

AF:

0.0534

AC:

13295

AN:

248770

AF XY:

0.0483

show subpopulations

Gnomad AFR exome

AF:

0.00899

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0248

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0353

AC:

51615

AN:

1461632

Hom.:

2056

Cov.:

AF XY:

0.0340

AC XY:

24739

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00636

AC:

213

AN:

33476

American (AMR)

AF:

0.112

AC:

5000

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

241

AN:

26132

East Asian (EAS)

AF:

0.227

AC:

9000

AN:

39676

South Asian (SAS)

AF:

0.0167

AC:

1442

AN:

86250

European-Finnish (FIN)

AF:

0.0327

AC:

1744

AN:

53396

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0282

AC:

31405

AN:

1111832

Other (OTH)

AF:

0.0420

AC:

2537

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2719

5437

8156

10874

13593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1402

2804

4206

5608

7010

<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:

0.0350

AC:

5327

AN:

152236

Hom.:

286

Cov.:

AF XY:

0.0375

AC XY:

2792

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00914

AC:

380

AN:

41562

American (AMR)

AF:

0.0900

AC:

1375

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.262

AC:

1356

AN:

5172

South Asian (SAS)

AF:

0.0215

AC:

104

AN:

4826

European-Finnish (FIN)

AF:

0.0319

AC:

338

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0246

AC:

1671

AN:

68018

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

239

479

718

958

1197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0243

Hom.:

Bravo

AF:

0.0395

TwinsUK

AF:

0.0294

AC:

109

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00924

AC:

ESP6500EA

AF:

0.0264

AC:

215

ExAC

AF:

0.0471

AC:

5690

Asia WGS

AF:

0.120

AC:

414

AN:

3478

EpiCase

AF:

0.0214

EpiControl

AF:

0.0220

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 31, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

JMJD1C-related disorder

Benign:1

Mar 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Early myoclonic encephalopathy

Benign:1

Feb 03, 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

0.081

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0054

.;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;.

PhyloP100

1.3

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.19

.;N;N

REVEL

Benign

0.11

Sift

Benign

0.24

.;T;T

Sift4G

Benign

0.86

.;T;T

Polyphen

0.0020

.;B;.

Vest4

0.019, 0.034

MutPred

0.11

.;Gain of phosphorylation at T513 (P = 0.1277);.;

MPC

0.060

ClinPred

0.016

GERP RS

4.1

Varity_R

0.033

gMVP

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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