Variant rs201497554 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.959G>A(p.Ser320Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,613,550 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.26

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:

JMJD1C (HGNC:):

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=0.015464008).

BP6

Variant 10-63215319-C-T is Benign according to our data. Variant chr10-63215319-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460283.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-63215319-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3 linkuse as main transcript	c.959G>A	p.Ser320Asn	missense_variant	7/26	ENST00000399262.7	NP_116165.1	Q15652-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JMJD1C	ENST00000399262.7 linkuse as main transcript	c.959G>A	p.Ser320Asn	missense_variant	7/26	5	NM_032776.3	ENSP00000382204.2	Q15652-1
JMJD1C	ENST00000542921.5 linkuse as main transcript	c.413G>A	p.Ser138Asn	missense_variant	6/25	1		ENSP00000444682.1	Q15652-3
JMJD1C	ENST00000402544.5 linkuse as main transcript	n.931G>A		non_coding_transcript_exon_variant	4/22	1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

171

AN:

151642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00183

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00121

AC:

303

AN:

249480

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00218

Gnomad NFE exome

AF:

0.00159

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.00125

AC:

1830

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

933

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00140

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00113

AC:

171

AN:

151748

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00183

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.000933

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.00158

AC:

ExAC

AF:

0.00113

AC:

137

EpiCase

AF:

0.00104

EpiControl

AF:

0.00148

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

.;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.19

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.11

.;T;T

Polyphen

1.0

.;D;.

Vest4

0.55, 0.51

MVP

0.62

MPC

0.39

ClinPred

0.063

GERP RS

5.6

Varity_R

0.39

gMVP

0.35

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