rs71508957

Variant names:

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.7591G>A(p.Glu2531Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,603,916 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E2531E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0047 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 55 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.64

Publications

19 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=0.004607469).

BP6

Variant 10-63168077-C-T is Benign according to our data. Variant chr10-63168077-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 460278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 714 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD1C	NM_032776.3	MANE Select	c.7591G>A	p.Glu2531Lys	missense	Exon 26 of 26	NP_116165.1	Q15652-1
JMJD1C	NM_001322252.2		c.7477G>A	p.Glu2493Lys	missense	Exon 25 of 25	NP_001309181.1
JMJD1C	NM_001282948.2		c.7045G>A	p.Glu2349Lys	missense	Exon 25 of 25	NP_001269877.1	Q15652-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.7591G>A	p.Glu2531Lys	missense	Exon 26 of 26	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5	TSL:1	c.7045G>A	p.Glu2349Lys	missense	Exon 25 of 25	ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5	TSL:1	n.7282G>A		non_coding_transcript_exon	Exon 22 of 22

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00824

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00421

AC:

1047

AN:

248660

AF XY:

0.00435

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00165

Gnomad NFE exome

AF:

0.00676

Gnomad OTH exome

AF:

0.00696

GnomAD4 exome

AF:

0.00720

AC:

10445

AN:

1451682

Hom.:

Cov.:

AF XY:

0.00699

AC XY:

5055

AN XY:

722820

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

33308

American (AMR)

AF:

0.00253

AC:

113

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26040

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00291

AC:

250

AN:

86002

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

52788

Middle Eastern (MID)

AF:

0.00418

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00860

AC:

9492

AN:

1103470

Other (OTH)

AF:

0.00689

AC:

414

AN:

60044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

425

851

1276

1702

2127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.00469

AC:

714

AN:

152234

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

310

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41562

American (AMR)

AF:

0.00327

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00331

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00822

AC:

559

AN:

67994

Other (OTH)

AF:

0.00569

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

125

166

208

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:

0.00616

Hom.:

Bravo

AF:

0.00488

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00161

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00411

AC:

496

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00710

EpiControl

AF:

0.00682

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Early myoclonic encephalopathy (1)

JMJD1C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

PhyloP100

2.6

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.17

Sift

Benign

0.044

Sift4G

Uncertain

0.042

Polyphen

1.0

Vest4

0.63

MVP

0.65

MPC

2.0

ClinPred

0.018

GERP RS

5.4

Varity_R

0.30

gMVP

0.22

Mutation Taster

=91/9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over