rs201371848

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032776.3(JMJD1C):c.1166T>C(p.Ile389Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,601,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.385

Publications

2 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009141803).

BP6

Variant 10-63215001-A-G is Benign according to our data. Variant chr10-63215001-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 577996.

BS2

High AC in GnomAd4 at 48 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.1166T>C	p.Ile389Thr	missense	Exon 8 of 26	NP_116165.1	Q15652-1
JMJD1C	NM_001322252.2		c.1052T>C	p.Ile351Thr	missense	Exon 7 of 25	NP_001309181.1
JMJD1C	NM_001282948.2		c.620T>C	p.Ile207Thr	missense	Exon 7 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.1166T>C	p.Ile389Thr	missense	Exon 8 of 26	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5	TSL:1	c.620T>C	p.Ile207Thr	missense	Exon 7 of 25	ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5	TSL:1	n.1138T>C		non_coding_transcript_exon	Exon 5 of 22

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000656

AC:

AN:

243790

AF XY:

0.0000530

show subpopulations

Gnomad AFR exome

AF:

0.000911

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1449324

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

720994

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

32928

American (AMR)

AF:

0.00

AC:

AN:

43800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.00

AC:

AN:

83762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104782

Other (OTH)

AF:

0.0000167

AC:

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000316

AC:

AN:

151882

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

41328

American (AMR)

AF:

0.0000656

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.0000874

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.00195

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Early myoclonic encephalopathy (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.5

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.75

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.67

PhyloP100

0.39

PrimateAI

Benign

0.35

PROVEAN

Benign

0.67

REVEL

Benign

0.024

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.030

MVP

0.068

MPC

0.082

ClinPred

0.0014

GERP RS

0.45

Varity_R

0.023

gMVP

0.032

Mutation Taster

=94/6

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