10-63267098-G-C

Variant names:

• chr10-63267098-G-C
• rs10995485
• NM_032776.3:c.334-2334C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032776.3(JMJD1C):​c.334-2334C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 152,176 control chromosomes in the GnomAD database, including 33 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 0.016 (33 hom., cov: 32)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 4 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0162 (2471/152176) while in subpopulation NFE AF = 0.0246 (1670/67974). AF 95% confidence interval is 0.0236. There are 33 homozygotes in GnomAd4. There are 1176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2471 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.334-2334C>G		intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.334-47115C>G		intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.-214+1565C>G		intron	N/A	NP_001269877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.334-2334C>G		intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.-214+1565C>G		intron	N/A	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.525+1565C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2472 AN: 152058 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0162 AC: 2471 AN: 152176 Hom.: 33 Cov.: 32 AF XY: 0.0158 AC XY: 1176 AN XY: 74410

African (AFR) AF: 0.00368 AC: 153 AN: 41536

American (AMR) AF: 0.0104 AC: 159 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.0306 AC: 324 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1670 AN: 67974

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.0190 Hom.: 2

Bravo AF: 0.0142

Asia WGS AF: 0.00173 AC: 6 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.46
DANN	Benign	0.61
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs10995485; hg19: chr10-65026858;