Genetic Variant JMJD1C:p.Met460Thr (chr10-63214788-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032776.3(JMJD1C):c.1379T>C(p.Met460Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,613,670 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 224 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.628

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015247464).

BP6

Variant 10-63214788-A-G is Benign according to our data. Variant chr10-63214788-A-G is described in ClinVar as [Benign]. Clinvar id is 460214.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00846 (1287/152164) while in subpopulation EAS AF= 0.0375 (194/5176). AF 95% confidence interval is 0.0332. There are 46 homozygotes in gnomad4. There are 943 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1287 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3 link	c.1379T>C	p.Met460Thr	missense_variant	Exon 8 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.1379T>C	p.Met460Thr	missense_variant	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 link	c.833T>C	p.Met278Thr	missense_variant	Exon 7 of 25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 link	n.1351T>C		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1289

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0918

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0114

AC:

2838

AN:

248852

Hom.:

103

AF XY:

0.0108

AC XY:

1457

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.0350

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00877

GnomAD4 exome

AF:

0.00466

AC:

6811

AN:

1461506

Hom.:

224

Cov.:

AF XY:

0.00451

AC XY:

3280

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0395

Gnomad4 SAS exome

AF:

0.000475

Gnomad4 FIN exome

AF:

0.0809

Gnomad4 NFE exome

AF:

0.000523

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00846

AC:

1287

AN:

152164

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

943

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.0375

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0918

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00173

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00183

AC:

ExAC

AF:

0.0100

AC:

1212

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.4

DANN

Benign

0.52

DEOGEN2

Benign

0.010

.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.48

.;N;N

REVEL

Benign

0.035

Sift

Benign

0.44

.;T;T

Sift4G

Benign

0.56

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.17, 0.11

MPC

0.075

ClinPred

0.0052

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.024

gMVP

0.13

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