Variant rs149889210 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032776.3(JMJD1C):c.1682C>G(p.Ser561Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,614,000 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 4 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.14

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00310418).

BP6

Variant 10-63214485-G-C is Benign according to our data. Variant chr10-63214485-G-C is described in ClinVar as [Benign]. Clinvar id is 460223.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 383 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3 linkuse as main transcript	c.1682C>G	p.Ser561Cys	missense_variant	8/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7 linkuse as main transcript	c.1682C>G	p.Ser561Cys	missense_variant	8/26	5	NM_032776.3		Q15652-1
JMJD1C	ENST00000542921.5 linkuse as main transcript	c.1136C>G	p.Ser379Cys	missense_variant	7/25	1		P1	Q15652-3
JMJD1C	ENST00000402544.5 linkuse as main transcript	n.1654C>G		non_coding_transcript_exon_variant	5/22	1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

383

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00902

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000756

AC:

188

AN:

248772

Hom.:

AF XY:

0.000600

AC XY:

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000278

AC:

406

AN:

1461674

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

169

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152326

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00900

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000959

Hom.:

Bravo

AF:

0.00295

ESP6500AA

AF:

0.00927

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000886

AC:

107

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early myoclonic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.79

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.34

Polyphen

0.0010

.;B;.

Vest4

0.11, 0.12

MVP

0.24

MPC

0.066

ClinPred

0.010

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over