NM_032776.3:c.5396T>G

Variant names:

• chr10-63198608-A-C
• NM_032776.3:c.5396T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032776.3(JMJD1C):​c.5396T>G​(p.Ile1799Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30614987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.5396T>G	p.Ile1799Arg	missense_variant	Exon 12 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.5396T>G	p.Ile1799Arg	missense_variant	Exon 12 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.4850T>G	p.Ile1617Arg	missense_variant	Exon 11 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.5166T>G		non_coding_transcript_exon_variant	Exon 8 of 22	1
JMJD1C	ENST00000327520.7	c.1130-1045T>G		intron_variant	Intron 1 of 11	2		ENSP00000335929.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454482 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	.;T;.
Eigen	Benign	-0.015
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	.;N;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	.;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.0040	.;D;D
Polyphen		0.070	.;B;.
Vest4		0.68, 0.47
MutPred		0.36		.;Gain of disorder (P = 0.0264);.;
MVP		0.71
MPC		2.3
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.66
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-64958368;