NM_032776.3:c.2695-6_2695-5insGTTTTGTTTTGTTTTGTT

Variant names:

• chr10-63209240-T-TAACAAAACAAAACAAAAC
• rs60227922
• NM_032776.3:c.2695-6_2695-5insGTTTTGTTTTGTTTTGTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_032776.3(JMJD1C):​c.2695-6_2695-5insGTTTTGTTTTGTTTTGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.2695-6_2695-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.2581-6_2581-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.2149-6_2149-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A	NP_001269877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.2695-6_2695-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.2149-6_2149-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.2667-6_2667-5insGTTTTGTTTTGTTTTGTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs60227922; hg19: chr10-64969000;