Genetic Variant JMJD1C:c.334-56203A>G (chr10-63320967-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032776.3(JMJD1C):c.334-56203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,988 control chromosomes in the GnomAD database, including 14,409 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14409 hom., cov: 32)

Consequence

JMJD1C
NM_032776.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
JMJD1C	NM_032776.3	MANE Select	c.334-56203A>G	intron	N/A	NP_116165.1	Q15652-1
JMJD1C	NM_001322252.2		c.333+59351A>G	intron	N/A	NP_001309181.1
JMJD1C	NM_001318154.2		c.-213-56203A>G	intron	N/A	NP_001305083.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.334-56203A>G		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C	ENST00000633035.1	TSL:3	n.279-56203A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64729

AN:

151870

Hom.:

14421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.427

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.426

AC:

64702

AN:

151988

Hom.:

14409

Cov.:

AF XY:

0.425

AC XY:

31573

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.327

AC:

13551

AN:

41466

American (AMR)

AF:

0.344

AC:

5257

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2036

AN:

3470

East Asian (EAS)

AF:

0.333

AC:

1715

AN:

5156

South Asian (SAS)

AF:

0.531

AC:

2559

AN:

4818

European-Finnish (FIN)

AF:

0.463

AC:

4876

AN:

10538

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33110

AN:

67946

Other (OTH)

AF:

0.424

AC:

894

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1905

3810

5714

7619

9524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.321

Hom.:

927

Bravo

AF:

0.404

Asia WGS

AF:

0.408

AC:

1421

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.7

(source)

DANN

Benign

0.89

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over