rs41274068

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032776.3(JMJD1C):c.1949C>T(p.Thr650Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,936 control chromosomes in the GnomAD database, including 161 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T650T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0086 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 152 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.27

Publications

10 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00345847).

BP6

Variant 10-63214218-G-A is Benign according to our data. Variant chr10-63214218-G-A is described in ClinVar as Benign. ClinVar VariationId is 460226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1310 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.1949C>T	p.Thr650Ile	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.1949C>T	p.Thr650Ile	missense_variant	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.1403C>T	p.Thr468Ile	missense_variant	Exon 7 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.1921C>T		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes

AF:

0.00864

AC:

1314

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00874

AC:

2178

AN:

249102

AF XY:

0.00878

show subpopulations

Gnomad AFR exome

AF:

0.00239

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00909

GnomAD4 exome

AF:

0.0123

AC:

17906

AN:

1461658

Hom.:

152

Cov.:

AF XY:

0.0120

AC XY:

8705

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00251

AC:

AN:

33480

American (AMR)

AF:

0.00344

AC:

154

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00429

AC:

112

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00325

AC:

280

AN:

86254

European-Finnish (FIN)

AF:

0.0174

AC:

927

AN:

53280

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0142

AC:

15762

AN:

1111940

Other (OTH)

AF:

0.00954

AC:

576

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

987

1973

2960

3946

4933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.00860

AC:

1310

AN:

152278

Hom.:

Cov.:

AF XY:

0.00880

AC XY:

655

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00294

AC:

122

AN:

41562

American (AMR)

AF:

0.00360

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0132

AC:

900

AN:

68004

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

133

199

266

332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0115

Hom.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00266

AC:

ESP6500EA

AF:

0.0132

AC:

108

ExAC

AF:

0.00858

AC:

1037

Asia WGS

AF:

0.00173

AC:

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

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

JMJD1C: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Early myoclonic encephalopathy

Benign:1

Jan 30, 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

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0071

.;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.

PhyloP100

2.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.0

.;N;N

REVEL

Benign

0.022

Sift

Uncertain

0.020

.;D;D

Sift4G

Benign

0.21

.;T;T

Polyphen

0.12

.;B;.

Vest4

0.18, 0.19

MVP

0.36

MPC

0.085

ClinPred

0.0081

GERP RS

3.1

Varity_R

0.034

gMVP

0.10

Mutation Taster

=99/1

polymorphism

(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