NM_032776.3:c.333+27282A>C

Variant names:

• chr10-63353036-T-G
• rs10822160
• NM_032776.3:c.333+27282A>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.333+27282A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,956 control chromosomes in the GnomAD database, including 14,372 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 (14372 hom., cov: 31)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.333+27282A>C		intron_variant	Intron 2 of 25	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.333+27282A>C		intron_variant	Intron 2 of 25	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000633035.1	n.278+27282A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64644 AN: 151838 Hom.: 14384 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.425 AC: 64618 AN: 151956 Hom.: 14372 Cov.: 31 AF XY: 0.425 AC XY: 31560 AN XY: 74274

African (AFR) AF: 0.326 AC: 13511 AN: 41436

American (AMR) AF: 0.344 AC: 5257 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1696 AN: 5158

South Asian (SAS) AF: 0.531 AC: 2562 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4877 AN: 10552

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33088 AN: 67946

Other (OTH) AF: 0.422 AC: 889 AN: 2106

Alfa AF: 0.321 Hom.: 929

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		0.33
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: rs10822160; hg19: chr10-65112796;