chr10-63214299-A-G

Position:

chr10-63214299-A-G

Variant summary

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

The NM_032776.3(JMJD1C):c.1868T>C(p.Ile623Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,614,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.83

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=0.00728181).

BP6

Variant 10-63214299-A-G is Benign according to our data. Variant chr10-63214299-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 529726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 157 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3 linkuse as main transcript	c.1868T>C	p.Ile623Thr	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.1868T>C	p.Ile623Thr	missense_variant	8/26	5	NM_032776.3	ENSP00000382204		Q15652-1
JMJD1C	ENST00000542921.5 linkuse as main transcript	c.1322T>C	p.Ile441Thr	missense_variant	7/25	1		ENSP00000444682	P1	Q15652-3
JMJD1C	ENST00000402544.5 linkuse as main transcript	n.1840T>C		non_coding_transcript_exon_variant	5/22	1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000305

AC:

AN:

249242

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.000319

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1461738

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152312

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00366

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.00132

ESP6500AA

AF:

0.00352

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000323

AC:

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

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 04, 2023

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Early myoclonic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0092

.;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L;.

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.68

.;N;N

REVEL

Benign

0.068

Sift

Benign

0.052

.;T;T

Sift4G

Benign

0.28

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.073, 0.041

MVP

0.19

MPC

0.082

ClinPred

0.013

GERP RS

3.8

Varity_R

0.054

gMVP

0.052

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