rs41274072

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.1771A>G(p.Met591Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 1,613,846 control chromosomes in the GnomAD database, including 1,181 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 (★★).

Frequency

Genomes: 𝑓 0.051 ( 298 hom., cov: 32)

Exomes 𝑓: 0.031 ( 883 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.355

Publications

12 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=0.0013146698).

BP6

Variant 10-63214396-T-C is Benign according to our data. Variant chr10-63214396-T-C is described in ClinVar as Benign. ClinVar VariationId is 460225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.1771A>G	p.Met591Val	missense_variant	Exon 8 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
JMJD1C	ENST00000399262.7 link	c.1771A>G	p.Met591Val	missense_variant	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5 link	c.1225A>G	p.Met409Val	missense_variant	Exon 7 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5 link	n.1743A>G		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7769

AN:

152220

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.0430

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0289

AC:

7204

AN:

248896

AF XY:

0.0267

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.00845

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0435

Gnomad NFE exome

AF:

0.0329

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0306

AC:

44768

AN:

1461508

Hom.:

883

Cov.:

AF XY:

0.0295

AC XY:

21441

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.112

AC:

3765

AN:

33470

American (AMR)

AF:

0.0163

AC:

730

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00949

AC:

248

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00333

AC:

287

AN:

86244

European-Finnish (FIN)

AF:

0.0435

AC:

2312

AN:

53210

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0319

AC:

35464

AN:

1111896

Other (OTH)

AF:

0.0310

AC:

1871

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2346

4692

7037

9383

11729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1302

2604

3906

5208

6510

<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:

0.0512

AC:

7796

AN:

152338

Hom.:

298

Cov.:

AF XY:

0.0498

AC XY:

3711

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.108

AC:

4468

AN:

41558

American (AMR)

AF:

0.0278

AC:

425

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0430

AC:

457

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0339

AC:

2304

AN:

68030

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

383

766

1149

1532

1915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0370

Hom.:

513

Bravo

AF:

0.0535

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0324

AC:

125

ESP6500AA

AF:

0.107

AC:

401

ESP6500EA

AF:

0.0308

AC:

254

ExAC

AF:

0.0316

AC:

3816

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0290

EpiControl

AF:

0.0283

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 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

0.059

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.3

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0071

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.

PhyloP100

-0.35

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.17

.;N;N

REVEL

Benign

0.060

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.23

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.031, 0.017

MPC

0.067

ClinPred

0.0058

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.019

gMVP

0.075

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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