chr10-63208774-T-C

Variant names:

• chr10-63208774-T-C
• rs189118006
• NM_032776.3:c.2895A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032776.3(JMJD1C):​c.2895A>G​(p.Glu965Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,816 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: 0.0000014 (0 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.2895A>G	p.Glu965Glu	synonymous_variant	Exon 10 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.2895A>G	p.Glu965Glu	synonymous_variant	Exon 10 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.2349A>G	p.Glu783Glu	synonymous_variant	Exon 9 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.2867A>G		non_coding_transcript_exon_variant	Exon 7 of 22	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438816 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 714846

African (AFR) AF: 0.00 AC: 0 AN: 32076

American (AMR) AF: 0.0000264 AC: 1 AN: 37880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 81706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104920

Other (OTH) AF: 0.00 AC: 0 AN: 59394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs189118006; hg19: chr10-64968534;