NM_032776.3:c.447+17955A>G

Variant names:

• chr10-63246696-T-C
• rs6479891
• NM_032776.3:c.447+17955A>G

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+17955A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,008 control chromosomes in the GnomAD database, including 56,845 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 0.86 (56845 hom., cov: 30)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 20 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.447+17955A>G		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+17955A>G		intron_variant	Intron 3 of 25	5	NM_032776.3	ENSP00000382204.2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130569 AN: 151890 Hom.: 56810 Cov.: 30

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.859 AC: 130648 AN: 152008 Hom.: 56845 Cov.: 30 AF XY: 0.856 AC XY: 63566 AN XY: 74276

African (AFR) AF: 0.960 AC: 39855 AN: 41508

American (AMR) AF: 0.706 AC: 10779 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3065 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3352 AN: 5144

South Asian (SAS) AF: 0.770 AC: 3710 AN: 4816

European-Finnish (FIN) AF: 0.868 AC: 9126 AN: 10514

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58029 AN: 67974

Other (OTH) AF: 0.827 AC: 1744 AN: 2108

Alfa AF: 0.850 Hom.: 124341

Bravo AF: 0.848

Asia WGS AF: 0.704 AC: 2447 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.2
DANN	Benign	0.11
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs6479891; hg19: chr10-65006456;