NM_032776.3:c.5939C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032776.3(JMJD1C):c.5939C>T(p.Pro1980Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0344 in 1,613,898 control chromosomes in the GnomAD database, including 1,144 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1980R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1079 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.13

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=0.0031484067).

BP6

Variant 10-63193075-G-A is Benign according to our data. Variant chr10-63193075-G-A is described in ClinVar as Benign. ClinVar VariationId is 460262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0241 (3662/152206) while in subpopulation NFE AF = 0.0392 (2663/68012). AF 95% confidence interval is 0.0379. There are 65 homozygotes in GnomAd4. There are 1606 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3662 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.5939C>T	p.Pro1980Leu	missense_variant	Exon 16 of 26	ENST00000399262.7	NP_116165.1	Q15652-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7 link	c.5939C>T	p.Pro1980Leu	missense_variant	Exon 16 of 26	5	NM_032776.3	ENSP00000382204.2		Q15652-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3662

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00570

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0392

Gnomad OTH

AF:

0.0291

GnomAD2 exomes

AF:

0.0253

AC:

6305

AN:

249414

AF XY:

0.0260

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0312

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0355

AC:

51858

AN:

1461692

Hom.:

1079

Cov.:

AF XY:

0.0350

AC XY:

25455

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00606

AC:

203

AN:

33474

American (AMR)

AF:

0.0136

AC:

607

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0299

AC:

782

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0150

AC:

1298

AN:

86254

European-Finnish (FIN)

AF:

0.0191

AC:

1020

AN:

53380

Middle Eastern (MID)

AF:

0.0255

AC:

147

AN:

5768

European-Non Finnish (NFE)

AF:

0.0412

AC:

45825

AN:

1111876

Other (OTH)

AF:

0.0327

AC:

1975

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2625

5251

7876

10502

13127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1708

3416

5124

6832

8540

<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:

0.0241

AC:

3662

AN:

152206

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00568

AC:

236

AN:

41516

American (AMR)

AF:

0.0239

AC:

365

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0154

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0143

AC:

151

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0392

AC:

2663

AN:

68012

Other (OTH)

AF:

0.0288

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

182

364

546

728

910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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.:

344

Bravo

AF:

0.0245

TwinsUK

AF:

0.0440

AC:

163

ALSPAC

AF:

0.0433

AC:

167

ESP6500AA

AF:

0.00607

AC:

ESP6500EA

AF:

0.0350

AC:

289

ExAC

AF:

0.0252

AC:

3040

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0382

EpiControl

AF:

0.0391

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

0.061

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0088

.;T;.

Eigen

Benign

-0.087

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.

PhyloP100

5.1

PrimateAI

Benign

0.32

PROVEAN

Benign

0.24

.;N;N

REVEL

Benign

0.063

Sift

Benign

0.068

.;T;D

Sift4G

Benign

0.13

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.090, 0.15

MPC

0.14

ClinPred

0.015

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.15

Mutation Taster

=99/1

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