10-63275024-T-C

Position:

• chr10-63275024-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.334-10260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,928 control chromosomes in the GnomAD database, including 36,113 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 0.66 (36113 hom., cov: 31)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.334-10260A>G		intron_variant		ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.334-10260A>G		intron_variant		5	NM_032776.3	ENSP00000382204
JMJD1C	ENST00000633035.1	n.279-10260A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100915 AN: 151810 Hom.: 36135 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.664 AC: 100884 AN: 151928 Hom.: 36113 Cov.: 31 AF XY: 0.666 AC XY: 49482 AN XY: 74256

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.653

Alfa AF: 0.588 Hom.: 1497

Bravo AF: 0.631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.55

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: rs10761733; hg19: chr10-65034784;