dbSNP rs79059103: JMJD1C:p.Leu2316Leu (chr10-63184621-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032776.3(JMJD1C):c.6948G>A(p.Leu2316Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000535 in 1,608,164 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 4 hom. )

Consequence

JMJD1C
NM_032776.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.667

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 10-63184621-C-T is Benign according to our data. Variant chr10-63184621-C-T is described in ClinVar as [Benign]. Clinvar id is 460274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.667 with no splicing effect.

BS2

High AC in GnomAd4 at 401 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.6948G>A	p.Leu2316Leu	synonymous_variant	Exon 21 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.6948G>A	p.Leu2316Leu	synonymous_variant	Exon 21 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.6402G>A	p.Leu2134Leu	synonymous_variant	Exon 20 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.6664G>A		non_coding_transcript_exon_variant	Exon 17 of 22	1
JMJD1C	ENST00000327520.7 link	c.2586G>A	p.Leu862Leu	synonymous_variant	Exon 10 of 12	2		ENSP00000335929.5	H7BXU7

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

404

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.0000735

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000690

AC:

168

AN:

243524

Hom.:

AF XY:

0.000537

AC XY:

AN XY:

132176

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000315

AC:

459

AN:

1455898

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

194

AN XY:

724232

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000881

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152266

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00898

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00300

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: 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: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

4.6

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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