NM_032776.3:c.447+11724T>C

Variant names:

• chr10-63252927-A-G
• rs4400684
• NM_032776.3:c.447+11724T>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.447+11724T>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 152,118 control chromosomes in the GnomAD database, including 14,415 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 (14415 hom., cov: 33)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.447+11724T>C		intron_variant	Intron 3 of 25	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.447+11724T>C		intron_variant	Intron 3 of 25	5	NM_032776.3	ENSP00000382204.2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64778 AN: 152002 Hom.: 14428 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.426 AC: 64749 AN: 152118 Hom.: 14415 Cov.: 33 AF XY: 0.425 AC XY: 31612 AN XY: 74354

African (AFR) AF: 0.326 AC: 13537 AN: 41504

American (AMR) AF: 0.344 AC: 5257 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1728 AN: 5174

South Asian (SAS) AF: 0.532 AC: 2567 AN: 4824

European-Finnish (FIN) AF: 0.462 AC: 4885 AN: 10570

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33141 AN: 67980

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.347 Hom.: 2005

Bravo AF: 0.404

Asia WGS AF: 0.409 AC: 1421 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		-0.72
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: rs4400684; hg19: chr10-65012687;