rs201112543

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.56T>A(p.Val19Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,609,330 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.491

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:

JMJD1C-AS1 (HGNC:28222): (JMJD1C antisense RNA 1)

JMJD1C-AS1 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=0.0060442984).

BP6

Variant 10-63465607-A-T is Benign according to our data. Variant chr10-63465607-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 460261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 349 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.56T>A	p.Val19Asp	missense_variant	Exon 1 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.56T>A	p.Val19Asp	missense_variant	Exon 1 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C-AS1	ENST00000609436.1 link	n.379A>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
JMJD1C	ENST00000633035.1 link	n.113+56131T>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

352

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000589

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000580

AC:

139

AN:

239512

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

131194

show subpopulations

Gnomad AFR exome

AF:

0.00868

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000929

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.000242

AC:

352

AN:

1457322

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

725270

show subpopulations

Gnomad4 AFR exome

AF:

0.00920

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00230

AC:

349

AN:

152008

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00786

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.00255

ESP6500AA

AF:

0.00667

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000701

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

JMJD1C-related disorder

Benign:1

Jun 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Early myoclonic encephalopathy

Benign:1

Jan 27, 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

0.095

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.011

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.20

REVEL

Benign

0.056

Sift

Benign

0.15

Sift4G

Benign

0.067

Polyphen

0.23

Vest4

0.28

MVP

0.37

MPC

0.11

ClinPred

0.031

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.10

gMVP

0.41

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