dbSNP rs201787760: JMJD1C:p.Glu2038Gln (chr10-63191073-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_032776.3(JMJD1C):c.6112G>C(p.Glu2038Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000662 in 1,613,884 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:2B:1

Conservation

PhyloP100: 7.13

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=0.005851269).

BP6

Variant 10-63191073-C-G is Benign according to our data. Variant chr10-63191073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 460265.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.6112G>C	p.Glu2038Gln	missense_variant	Exon 17 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.6112G>C	p.Glu2038Gln	missense_variant	Exon 17 of 26	5	NM_032776.3	ENSP00000382204.2		Q15652-1

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000409

AC:

102

AN:

249498

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000715

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000636

AC:

930

AN:

1461574

Hom.:

Cov.:

AF XY:

0.000656

AC XY:

477

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000756

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152310

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.000774

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000734

AC:

ExAC

AF:

0.000455

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Early myoclonic encephalopathy

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.0

.;M;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

.;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0040

.;D;D

Sift4G

Uncertain

0.0080

.;D;D

Polyphen

1.0

.;D;.

Vest4

0.46, 0.47

MVP

0.62

MPC

0.60

ClinPred

0.074

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.34

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