rs200016210

chr10-63215047-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_032776.3(JMJD1C):c.1120G>C(p.Asp374His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,608,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (1 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 7.48

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08754057).
• BP6: Variant 10-63215047-C-G is Benign according to our data. Variant chr10-63215047-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 460212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 87 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.1120G>C	p.Asp374His	missense_variant	8/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.1120G>C	p.Asp374His	missense_variant	8/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.574G>C	p.Asp192His	missense_variant	7/25	1		P1
JMJD1C	ENST00000402544.5	n.1092G>C		non_coding_transcript_exon_variant	5/22	1

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000476 AC: 117 AN: 245626 Hom.: 0 AF XY: 0.000465 AC XY: 62 AN XY: 133286

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.000891

Gnomad NFE exome AF: 0.000760

Gnomad OTH exome AF: 0.000834

GnomAD4 exome AF: 0.000596 AC: 868 AN: 1455926 Hom.: 1 Cov.: 32 AF XY: 0.000580 AC XY: 420 AN XY: 723948

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000238

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.000688

Gnomad4 OTH exome AF: 0.000498

GnomAD4 genome AF: 0.000572 AC: 87 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74428

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000473

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000254 Hom.: 0

Bravo AF: 0.000510

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000615 AC: 5

ExAC AF: 0.000621 AC: 75

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2023

- -

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpreted as Uncertain significance and reported on 01-03-2018 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	26
Dann	Uncertain	0.99
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.63	T
Polyphen		1.0	.;D;.
Vest4		0.81, 0.77
MVP		0.56
MPC		0.44
ClinPred		0.090	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.33

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

Other links and lift over

dbSNP: rs200016210; hg19: chr10-64974807; COSMIC: COSV67865933; COSMIC: COSV67865933;