Variant rs528244230 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.1112A>G(p.Asn371Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000803 in 1,607,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009602249).

BP6

Variant 10-63215055-T-C is Benign according to our data. Variant chr10-63215055-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 460211.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3 linkuse as main transcript	c.1112A>G	p.Asn371Ser	missense_variant	8/26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7 linkuse as main transcript	c.1112A>G	p.Asn371Ser	missense_variant	8/26	5	NM_032776.3	ENSP00000382204		Q15652-1
JMJD1C	ENST00000542921.5 linkuse as main transcript	c.566A>G	p.Asn189Ser	missense_variant	7/25	1		ENSP00000444682	P1	Q15652-3
JMJD1C	ENST00000402544.5 linkuse as main transcript	n.1084A>G		non_coding_transcript_exon_variant	5/22	1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

243570

Hom.:

AF XY:

0.000182

AC XY:

AN XY:

132102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00178

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000845

AC:

123

AN:

1454770

Hom.:

Cov.:

AF XY:

0.0000857

AC XY:

AN XY:

723320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00235

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000174

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early myoclonic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.

MutationTaster

Benign

0.90

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.051

Sift

Benign

0.12

.;T;T

Sift4G

Benign

0.61

.;T;T

Polyphen

0.86

.;P;.

Vest4

0.32, 0.35

MutPred

0.14

.;Gain of phosphorylation at N371 (P = 8e-04);.;

MVP

0.47

MPC

0.064

ClinPred

0.053

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.061

gMVP

0.042

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