rs186321056

Positions:

• chr10-63168075-C-A
• chr10-63168075-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032776.3(JMJD1C):​c.7593G>T​(p.Glu2531Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2531K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18543833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.7593G>T	p.Glu2531Asp	missense_variant	26/26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.7593G>T	p.Glu2531Asp	missense_variant	26/26	5	NM_032776.3	ENSP00000382204
JMJD1C	ENST00000542921.5	c.7047G>T	p.Glu2349Asp	missense_variant	25/25	1		ENSP00000444682	P1
JMJD1C	ENST00000402544.5	n.7284G>T		non_coding_transcript_exon_variant	22/22	1
JMJD1C	ENST00000467356.5	n.451G>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	.;T;.
Eigen	Benign	-0.025
Eigen_PC	Benign	0.0032
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.2	.;L;.
MutationTaster	Benign	0.81	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	.;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.020	.;D;D
Sift4G	Benign	0.086	.;T;T
Polyphen		0.98	.;D;.
Vest4		0.50, 0.48
MutPred		0.15		.;Loss of ubiquitination at K2528 (P = 0.0795);.;
MVP		0.89
MPC		1.6
ClinPred		0.90	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.17

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: rs186321056; hg19: chr10-64927835;