rs71508957

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032776.3(JMJD1C):c.7591G>A(p.Glu2531Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,603,916 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 55 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.64

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004607469).

BP6

Variant 10-63168077-C-T is Benign according to our data. Variant chr10-63168077-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-63168077-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 714 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.7591G>A	p.Glu2531Lys	missense_variant	Exon 26 of 26	ENST00000399262.7	NP_116165.1	Q15652-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
JMJD1C	ENST00000399262.7 link	c.7591G>A	p.Glu2531Lys	missense_variant	Exon 26 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.7045G>A	p.Glu2349Lys	missense_variant	Exon 25 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.7282G>A		non_coding_transcript_exon_variant	Exon 22 of 22	1
JMJD1C	ENST00000467356.5 link	n.449G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00824

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00421

AC:

1047

AN:

248660

Hom.:

AF XY:

0.00435

AC XY:

587

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00298

Gnomad FIN exome

AF:

0.00165

Gnomad NFE exome

AF:

0.00676

Gnomad OTH exome

AF:

0.00696

GnomAD4 exome

AF:

0.00720

AC:

10445

AN:

1451682

Hom.:

Cov.:

AF XY:

0.00699

AC XY:

5055

AN XY:

722820

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00291

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00860

Gnomad4 OTH exome

AF:

0.00689

GnomAD4 genome

AF:

0.00469

AC:

714

AN:

152234

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

310

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00822

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00632

Hom.:

Bravo

AF:

0.00488

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00161

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00411

AC:

496

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00710

EpiControl

AF:

0.00682

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

JMJD1C: BS2 -

JMJD1C-related disorder

Benign:1

May 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Early myoclonic encephalopathy

Benign:1

Jan 23, 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

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

.;T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

.;D;N

REVEL

Benign

0.17

Sift

Benign

0.044

.;D;T

Sift4G

Uncertain

0.042

.;D;D

Polyphen

1.0

.;D;.

Vest4

0.63, 0.61

MVP

0.65

MPC

2.0

ClinPred

0.018

GERP RS

5.4

Varity_R

0.30

gMVP

0.22

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