10-63302248-G-C

Variant names:

• chr10-63302248-G-C
• rs10761739
• NM_032776.3:c.334-37484C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399262.7(JMJD1C):​c.334-37484C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,956 control chromosomes in the GnomAD database, including 11,577 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 0.38 (11577 hom., cov: 32)
• Consequence: JMJD1C ENST00000399262.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399262.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.334-37484C>G		intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.333+78070C>G		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-213-37484C>G		intron	N/A	NP_001305083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.334-37484C>G		intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000633035.1	TSL:3	n.279-37484C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58404 AN: 151838 Hom.: 11585 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.384 AC: 58382 AN: 151956 Hom.: 11577 Cov.: 32 AF XY: 0.384 AC XY: 28482 AN XY: 74262

African (AFR) AF: 0.317 AC: 13145 AN: 41440

American (AMR) AF: 0.317 AC: 4832 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1715 AN: 5166

South Asian (SAS) AF: 0.500 AC: 2410 AN: 4818

European-Finnish (FIN) AF: 0.384 AC: 4046 AN: 10534

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28905 AN: 67962

Other (OTH) AF: 0.391 AC: 826 AN: 2114

Alfa AF: 0.401 Hom.: 1586

Bravo AF: 0.370

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.23
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: rs10761739; hg19: chr10-65062008;