10-63246696-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.447+17955A>G		intron_variant		ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.447+17955A>G		intron_variant		5	NM_032776.3

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

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.827

Alfa AF: 0.844 Hom.: 41840

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6479891; hg19: chr10-65006456;