10-63193075-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032776.3(JMJD1C):c.5939C>T(p.Pro1980Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0344 in 1,613,898 control chromosomes in the GnomAD database, including 1,144 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1980R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1079 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031484067).

BP6

Variant 10-63193075-G-A is Benign according to our data. Variant chr10-63193075-G-A is described in ClinVar as [Benign]. Clinvar id is 460262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-63193075-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0241 (3662/152206) while in subpopulation NFE AF= 0.0392 (2663/68012). AF 95% confidence interval is 0.0379. There are 65 homozygotes in gnomad4. There are 1606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3662 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.5939C>T	p.Pro1980Leu	missense_variant	Exon 16 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.5939C>T	p.Pro1980Leu	missense_variant	Exon 16 of 26	5	NM_032776.3	ENSP00000382204.2		Q15652-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3662

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00570

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0392

Gnomad OTH

AF:

0.0291

GnomAD3 exomes

AF:

0.0253

AC:

6305

AN:

249414

Hom.:

110

AF XY:

0.0260

AC XY:

3524

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0312

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0355

AC:

51858

AN:

1461692

Hom.:

1079

Cov.:

AF XY:

0.0350

AC XY:

25455

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0412

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0241

AC:

3662

AN:

152206

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00568

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.0392

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0330

Hom.:

182

Bravo

AF:

0.0245

TwinsUK

AF:

0.0440

AC:

163

ALSPAC

AF:

0.0433

AC:

167

ESP6500AA

AF:

0.00607

AC:

ESP6500EA

AF:

0.0350

AC:

289

ExAC

AF:

0.0252

AC:

3040

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0382

EpiControl

AF:

0.0391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Early myoclonic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0088

.;T;.

Eigen

Benign

-0.087

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.24

.;N;N

REVEL

Benign

0.063

Sift

Benign

0.068

.;T;D

Sift4G

Benign

0.13

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.090, 0.15

MPC

0.14

ClinPred

0.015

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.15

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