rs139881253

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.4180A>T(p.Thr1394Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000738 in 1,614,206 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 7 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.62

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=0.009985298).

BP6

Variant 10-63207489-T-A is Benign according to our data. Variant chr10-63207489-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 460244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000721 (1054/1461868) while in subpopulation MID AF = 0.0198 (114/5768). AF 95% confidence interval is 0.0168. There are 7 homozygotes in GnomAdExome4. There are 526 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 137 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.4180A>T	p.Thr1394Ser	missense_variant	Exon 10 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
JMJD1C	ENST00000399262.7 link	c.4180A>T	p.Thr1394Ser	missense_variant	Exon 10 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5 link	c.3634A>T	p.Thr1212Ser	missense_variant	Exon 9 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5 link	n.4152A>T		non_coding_transcript_exon_variant	Exon 7 of 22	1
JMJD1C	ENST00000327520.7 link	c.235A>T	p.Thr79Ser	missense_variant	Exon 1 of 12	2		ENSP00000335929.5

Frequencies

GnomAD3 genomes

AF:

0.000900

AC:

137

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000882

AC:

220

AN:

249348

AF XY:

0.000909

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000796

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.000721

AC:

1054

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000723

AC XY:

526

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33480

American (AMR)

AF:

0.00197

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00329

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000209

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5768

European-Non Finnish (NFE)

AF:

0.000548

AC:

609

AN:

1111990

Other (OTH)

AF:

0.00192

AC:

116

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000899

AC:

137

AN:

152338

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41584

American (AMR)

AF:

0.00366

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68018

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00104

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000260

AC:

ESP6500EA

AF:

0.000847

AC:

ExAC

AF:

0.000703

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

JMJD1C: BP4, BS1 -

Early myoclonic encephalopathy

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.2

.;M;.

PhyloP100

1.6

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.73

.;N;N

REVEL

Benign

0.050

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.59

.;T;T

Polyphen

0.97

.;D;.

Vest4

0.048, 0.055

MutPred

0.21

.;Loss of catalytic residue at T1394 (P = 0.1065);.;

MVP

0.49

MPC

0.062

ClinPred

0.029

GERP RS

3.3

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.19

gMVP

0.20

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