rs372806250

Positions:

• chr10-63208104-A-C
• chr10-63208104-A-G

Variant summary

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

The NM_032776.3(JMJD1C):​c.3565T>G​(p.Leu1189Val) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

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 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=0.13937345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.3565T>G	p.Leu1189Val	missense_variant	10/26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.3565T>G	p.Leu1189Val	missense_variant	10/26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.3019T>G	p.Leu1007Val	missense_variant	9/25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.3537T>G		non_coding_transcript_exon_variant	7/22	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;.
Eigen	Benign	0.025
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.81	.;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.011	.;D;D
Sift4G	Benign	0.40	.;T;T
Polyphen		0.93	.;P;.
Vest4		0.28, 0.27
MutPred		0.051		.;Gain of glycosylation at T1190 (P = 0.1072);.;
MVP		0.35
MPC		0.14
ClinPred		0.24	T
GERP RS		-1.3
Varity_R		0.12
gMVP		0.10

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: rs372806250; hg19: chr10-64967864;