10-63346791-G-T

Variant names:

• chr10-63346791-G-T
• rs7081275
• NM_032776.3:c.333+33527C>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.333+33527C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,164 control chromosomes in the GnomAD database, including 56,895 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 0.86 (56895 hom., cov: 32)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.333+33527C>A		intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.333+33527C>A		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-214+33527C>A		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.333+33527C>A		intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000633035.1	TSL:3	n.278+33527C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130694 AN: 152046 Hom.: 56861 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.859 AC: 130772 AN: 152164 Hom.: 56895 Cov.: 32 AF XY: 0.856 AC XY: 63632 AN XY: 74370

African (AFR) AF: 0.961 AC: 39896 AN: 41536

American (AMR) AF: 0.706 AC: 10774 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3067 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3358 AN: 5164

South Asian (SAS) AF: 0.770 AC: 3718 AN: 4828

European-Finnish (FIN) AF: 0.868 AC: 9184 AN: 10576

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58043 AN: 68022

Other (OTH) AF: 0.827 AC: 1744 AN: 2110

Alfa AF: 0.843 Hom.: 16375

Bravo AF: 0.848

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		0.25
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: rs7081275; hg19: chr10-65106551;