rs34798625

Variant names:

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.814G>A(p.Ala272Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00633 in 1,608,906 control chromosomes in the GnomAD database, including 97 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 0.013 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 68 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.525

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=0.0011672676).

BP6

Variant 10-63215561-C-T is Benign according to our data. Variant chr10-63215561-C-T is described in ClinVar as Benign. ClinVar VariationId is 460281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0133 (2031/152238) while in subpopulation AFR AF = 0.0338 (1403/41534). AF 95% confidence interval is 0.0323. There are 29 homozygotes in GnomAd4. There are 984 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2031 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.814G>A	p.Ala272Thr	missense_variant	Exon 6 of 26	ENST00000399262.7	NP_116165.1	Q15652-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7 link	c.814G>A	p.Ala272Thr	missense_variant	Exon 6 of 26	5	NM_032776.3	ENSP00000382204.2		Q15652-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2027

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00678

AC:

1684

AN:

248450

AF XY:

0.00653

show subpopulations

Gnomad AFR exome

AF:

0.0359

Gnomad AMR exome

AF:

0.00740

Gnomad ASJ exome

AF:

0.00290

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00647

GnomAD4 exome

AF:

0.00560

AC:

8161

AN:

1456668

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

4032

AN XY:

723588

show subpopulations

African (AFR)

AF:

0.0326

AC:

1086

AN:

33360

American (AMR)

AF:

0.00791

AC:

352

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00326

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.00864

AC:

744

AN:

86094

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00782

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00486

AC:

5387

AN:

1107812

Other (OTH)

AF:

0.00746

AC:

449

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

407

813

1220

1626

2033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0133

AC:

2031

AN:

152238

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

984

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0338

AC:

1403

AN:

41534

American (AMR)

AF:

0.0141

AC:

216

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00787

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00474

AC:

322

AN:

68004

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

196

295

393

491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00796

Hom.:

Bravo

AF:

0.0144

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.0328

AC:

124

ESP6500EA

AF:

0.00534

AC:

ExAC

AF:

0.00731

AC:

883

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00605

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

0.058

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.16

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0059

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

.;N;.

PhyloP100

-0.53

PrimateAI

Benign

0.25

PROVEAN

Benign

0.71

.;N;N

REVEL

Benign

0.081

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

.;T;T

Polyphen

0.0010

.;B;.

Vest4

0.036, 0.12

MVP

0.20

MPC

0.064

ClinPred

0.0010

GERP RS

-6.3

Varity_R

0.020

gMVP

0.094

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over