rs12355784

Positions:

• chr10-63361805-C-A
• chr10-63361805-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032776.3(JMJD1C):​c.333+18513G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 150,070 control chromosomes in the GnomAD database, including 14,370 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 (14370 hom., cov: 29)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.333+18513G>T		intron_variant		ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.333+18513G>T		intron_variant		5	NM_032776.3	ENSP00000382204
JMJD1C	ENST00000633035.1	n.278+18513G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64342 AN: 149980 Hom.: 14382 Cov.: 29

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.429 AC: 64315 AN: 150070 Hom.: 14370 Cov.: 29 AF XY: 0.428 AC XY: 31348 AN XY: 73184

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.426

Alfa AF: 0.472 Hom.: 19923

Bravo AF: 0.404

Asia WGS AF: 0.407 AC: 1413 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.31

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: rs12355784; hg19: chr10-65121565;