rs7923609

Variant names:

• chr10-63374062-A-G
• rs7923609
• NM_032776.3:c.333+6256T>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.333+6256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,054 control chromosomes in the GnomAD database, including 14,443 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 0.43 (14443 hom., cov: 32)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 47 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.333+6256T>C		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.333+6256T>C		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-214+6256T>C		intron	N/A	NP_001305083.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.333+6256T>C		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C	ENST00000633035.1	TSL:3	n.278+6256T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64860 AN: 151936 Hom.: 14456 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64833 AN: 152054 Hom.: 14443 Cov.: 32 AF XY: 0.426 AC XY: 31633 AN XY: 74306

African (AFR) AF: 0.329 AC: 13646 AN: 41506

American (AMR) AF: 0.345 AC: 5268 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2032 AN: 3464

East Asian (EAS) AF: 0.333 AC: 1724 AN: 5170

South Asian (SAS) AF: 0.532 AC: 2564 AN: 4820

European-Finnish (FIN) AF: 0.461 AC: 4861 AN: 10540

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33139 AN: 67954

Other (OTH) AF: 0.424 AC: 894 AN: 2110

Alfa AF: 0.467 Hom.: 77300

Bravo AF: 0.405

Asia WGS AF: 0.407 AC: 1407 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		1.1
Mutation Taster		=100/0	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: rs7923609; hg19: chr10-65133822;