rs34491125

Positions:

• chr10-63177741-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032776.3(JMJD1C):​c.7200C>G​(p.Asp2400Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,314 control chromosomes in the GnomAD database, including 995 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (66 hom., cov: 32)
  • Exomes 𝑓: 0.031 (929 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031909347).
• BP6: Variant 10-63177741-G-C is Benign according to our data. Variant chr10-63177741-G-C is described in ClinVar as [Benign]. Clinvar id is 460277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.7200C>G	p.Asp2400Glu	missense_variant	23/26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.7200C>G	p.Asp2400Glu	missense_variant	23/26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.6654C>G	p.Asp2218Glu	missense_variant	22/25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.6916C>G		non_coding_transcript_exon_variant	19/22	1
JMJD1C	ENST00000327520.7	c.2838C>G	p.Asp946Glu	missense_variant	12/12	2		ENSP00000335929.5

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3734 AN: 152144 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00685

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0373

GnomAD3 exomes AF: 0.0286 AC: 7128 AN: 249382 Hom.: 191 AF XY: 0.0320 AC XY: 4330 AN XY: 135302

Gnomad AFR exome AF: 0.00549

Gnomad AMR exome AF: 0.0154

Gnomad ASJ exome AF: 0.0858

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.0665

Gnomad FIN exome AF: 0.00742

Gnomad NFE exome AF: 0.0287

Gnomad OTH exome AF: 0.0334

GnomAD4 exome AF: 0.0309 AC: 45165 AN: 1461052 Hom.: 929 Cov.: 31 AF XY: 0.0325 AC XY: 23586 AN XY: 726838

Gnomad4 AFR exome AF: 0.00651

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0851

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0676

Gnomad4 FIN exome AF: 0.00757

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0336

GnomAD4 genome AF: 0.0245 AC: 3732 AN: 152262 Hom.: 66 Cov.: 32 AF XY: 0.0245 AC XY: 1824 AN XY: 74466

Gnomad4 AFR AF: 0.00683

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0327 Hom.: 88

Bravo AF: 0.0241

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0319 AC: 123

ESP6500AA AF: 0.00977 AC: 36

ESP6500EA AF: 0.0326 AC: 267

ExAC AF: 0.0284 AC: 3431

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.0328

EpiControl AF: 0.0320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Early myoclonic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	.;T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.63	T;T;T
MetaRNN	Benign	0.0032	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	.;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.14
Sift	Benign	0.31	.;T;T
Sift4G	Benign	0.54	.;T;T
Polyphen		0.48	.;P;.
Vest4		0.11, 0.18
MutPred		0.38		.;Loss of ubiquitination at K2397 (P = 0.0949);.;
MPC		1.3
ClinPred		0.013	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34491125; hg19: chr10-64937501; COSMIC: COSV59514358; COSMIC: COSV59514358;