10-63194199-C-G

Variant names:

• chr10-63194199-C-G
• rs2306264
• NM_032776.3:c.5734+87G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032776.3(JMJD1C):​c.5734+87G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 830,796 control chromosomes in the GnomAD database, including 28,526 homozygotes. 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: 𝑓 0.20 (4045 hom., cov: 32)
  • Exomes 𝑓: 0.25 (24481 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

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.5734+87G>C		intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.5620+87G>C		intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.5188+87G>C		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.5734+87G>C		intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.5188+87G>C		intron	N/A	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.5504+87G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30633 AN: 151984 Hom.: 4046 Cov.: 32

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.253 AC: 172035 AN: 678694 Hom.: 24481 AF XY: 0.253 AC XY: 92568 AN XY: 365516

African (AFR) AF: 0.0540 AC: 993 AN: 18380

American (AMR) AF: 0.159 AC: 6629 AN: 41784

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 5095 AN: 20678

East Asian (EAS) AF: 0.0153 AC: 549 AN: 35836

South Asian (SAS) AF: 0.196 AC: 13647 AN: 69582

European-Finnish (FIN) AF: 0.316 AC: 16017 AN: 50706

Middle Eastern (MID) AF: 0.263 AC: 1076 AN: 4096

European-Non Finnish (NFE) AF: 0.297 AC: 119603 AN: 403280

Other (OTH) AF: 0.245 AC: 8426 AN: 34352

GnomAD4 genome AF: 0.201 AC: 30627 AN: 152102 Hom.: 4045 Cov.: 32 AF XY: 0.201 AC XY: 14958 AN XY: 74348

African (AFR) AF: 0.0549 AC: 2282 AN: 41534

American (AMR) AF: 0.168 AC: 2574 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3468

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5188

South Asian (SAS) AF: 0.179 AC: 865 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3348 AN: 10532

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 20001 AN: 67954

Other (OTH) AF: 0.201 AC: 424 AN: 2114

Alfa AF: 0.131 Hom.: 258

Bravo AF: 0.188

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.39
PhyloP100		-1.4
Mutation Taster		=95/5	polymorphism (auto)

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: rs2306264; hg19: chr10-64953959;