10-63267850-A-T

Variant names:

• chr10-63267850-A-T
• rs10761731
• NM_032776.3:c.334-3086T>A

Variant summary

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

The NM_032776.3(JMJD1C):​c.334-3086T>A 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 151,978 control chromosomes in the GnomAD database, including 11,599 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 (11599 hom., cov: 31)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 102 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=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.334-3086T>A		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.334-47867T>A		intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.-214+813T>A		intron	N/A	NP_001269877.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.334-3086T>A		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C	ENST00000542921.5	TSL:1	c.-214+813T>A		intron	N/A	ENSP00000444682.1	Q15652-3
	JMJD1C	ENST00000402544.5	TSL:1	n.525+813T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58437 AN: 151860 Hom.: 11607 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.426

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: 58415 AN: 151978 Hom.: 11599 Cov.: 31 AF XY: 0.384 AC XY: 28482 AN XY: 74260

African (AFR) AF: 0.317 AC: 13129 AN: 41448

American (AMR) AF: 0.318 AC: 4847 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1944 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1700 AN: 5158

South Asian (SAS) AF: 0.502 AC: 2421 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4033 AN: 10554

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.426 AC: 28959 AN: 67956

Other (OTH) AF: 0.391 AC: 821 AN: 2102

Alfa AF: 0.421 Hom.: 7710

Bravo AF: 0.370

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.42
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: rs10761731; hg19: chr10-65027610;